Impact of primary care on hospital admission rates for diabetes patients: A systematic review.

High-quality primary care for diabetes patients may be related to lowered hospital admissions. A systematic search was performed to assess the impact of structure, process, and outcome of primary diabetes care on hospital admission rates, considering patient characteristics. Studies on diabetes patients in primary care with hospitalisation rates as outcomes published between January 1996 and December 2015 were included. Indicators of quality of care (access, continuity and structure of care, process, and outcome indicators) and patient characteristics (age, gender, ethnicity, insurance, socio-economic status, diabetes characteristics, co-morbidity, and health-related lifestyle) were extracted. After assessment of the strength of evidence, characteristics of care and diabetes patients were presented in relation to the likelihood of hospitalisation. Thirty-one studies were identified. A regular source of primary care and a well-controlled HbA1c level decreased the likelihood of hospitalisation. Other aspects of care were less consistent. Patients' age, co-morbidity, and socio-economic status were related to higher hospitalisation. Gender and health-related lifestyle showed no relationship. Studies were heterogeneous in design, sample, and healthcare system. Different definitions of diabetes and unscheduled admissions limited comparisons. In healthcare systems where diabetes patients have a regular source of primary care, hospital admission rates cannot be meaningfully related to primary care characteristics.

Do T1a breast cancers profit from adjuvant systemic therapy? A multicenter retrospective cohort study of 325 T1a-patients.

UNLABELLED: Small tumor size (≤5 mm, T1a) carries an excellent prognosis. Controversy exists over the extent of the variety of treatment approaches. We therefore explored the effect of adjuvant systemic therapy (AST) on recurrence free survival (RFS) and overall survival (OAS) for the group of T1a-tumors. METHODS: The multicenter study population included 9625 early breast cancer patients, diagnosed between 1992 and 2008. 5196 patients were T1 (54.0 %) and 325 of these patients (3.4 %) were T1a. RESULTS: Compared to patients with AST RFS and OAS were significantly worse for patients who did not receive AST (RFS: p = 0.001; OAS: p = 0.021). Even N0-T1a-patients (n = 279) significantly profited from AST (RFS: p = 0.001; OAS: p = 0.006). Patients with at least one poor prognostic factor (HR-, HER2+, N1 or G3) without AST also showed a significantly worse outcome (RFS: p = 0.026; OAS: p = 0.024) compared to pT1a-patients with AST. Consensus guidelines state that the prognosis of patients with T1a that are N0 is uncertain even if HER2 is amplified or overexpressed. In our study nodal-negative (N0) T1a-patients (n = 279) without AST showed a significantly worse RFS (p = 0.001), and a significantly worse OAS (p = 0.006) compared to those patients with AST. In multivariate analysis even after adjusting by age, grading, hormonal receptor status, HER2/neu-status and nodal status T1a-patients without AST were associated with a significantly worse RFS resp. OAS compared to patient with AST (RFS: p = 0.002; OAS: p = 0.007). CONCLUSIONS: There is an association between AST and improved RFS or OAS for breast cancer patients with T1a tumors.

Gender-Related Differences in Patients Presenting with Suspected Acute Coronary Syndromes: Clinical Presentation, Biomarkers and Diagnosis.

OBJECTIVES: Gender differences in patients presenting with suspected acute coronary syndromes (ACS) have not yet been fully characterized. The aim of this study was to assess gender-related disparities in clinical profiles, biomarkers and diagnoses of patients with suspected ACS. METHODS: This single-centre, prospective cohort study included 377 consecutive patients presenting with suspected ACS to the emergency department. Suspected ACS was defined as a request for conventional troponin T (c-cTnT) measurements on clinical grounds. RESULTS: Women were older than men (p = 0.004), and had a lower prevalence of known coronary artery and peripheral vascular disease (p < 0.05). c-cTnT was positive in 8% of female and in 14% of male patients (p = 0.16), TIMI risk score and cardiac biomarkers including c-cTnT, hs-cTnT, myoglobin, creatine kinase, N-terminal pro-brain natriuretic peptide, myeloid-related protein 8/14 and pregnancy-associated plasma protein A were lower in women (p < 0.05). Women were less frequently diagnosed with ACS (30 vs. 51%), and were not referred for urgent coronary angiography as often as men (p < 0.001). In multivariate analysis, female gender was associated with a lower referral for coronary angiography (HR 0.41, 95% CI 0.23-0.78, p = 0.006). CONCLUSIONS: In patients with suspected ACS, women presented with different biomarker profiles, and were less often diagnosed with ACS and referred to coronary angiography.

The impact of adjuvant radiotherapy on the survival of primary breast cancer patients: a retrospective multicenter cohort study of 8935 subjects.

BACKGROUND: Radiotherapy (RT) is proven to be an important backbone for adjuvant therapy in randomized, controlled trials, but it is unclear if these effects are provable in a daily routine cohort of breast cancer patients. This study sought to answer the following questions in a daily routine cohort of breast cancer patients: 1. Does guideline-adherent RT improve primary breast cancer patient survival? 2. Is breast-conserving surgery (BCS) followed by RT equal to a mastectomy (MA) with regard to outcome parameters? 3. Does adjuvant RT compensate for an incomplete tumor resection (R1)? PATIENTS AND METHODS: In this retrospective, multicenter cohort study, we investigated data from 8935 primary breast cancer patients recruited from 17 participating certified breast cancer centers in Germany between 1992 and 2008. Guideline adherence based on internationally validated guidelines. RESULTS: The patients who received guideline-adherent RT for primary breast cancer were associated with significantly improved survival parameters [recurrence-free survival (RFS): P < 0.001; overall survival (OS): P < 0.001] compared with patients who did not receive guideline-adherent adjuvant RT. Furthermore, the results demonstrated that there were no significant differences in RFS and OS between BCS followed by RT and MA [RFS: P = 0.293; OS: P = 0.104]. Adjuvant RT did not improve the outcome of patients receiving nonguideline-adherent incomplete tumor resection via BCS (R1); these patients showed a significantly impaired RFS [P < 0.001] and OS [P < 0.001] compared with patients who underwent guideline-adherent complete tumor resection via BCS (R0). In addition, non-guideline-adherent RT after MA (overtherapy) did not significantly influence survival [RFS: P = 0.838; OS: P = 0.613]. CONCLUSION: Our study confirms the importance of guideline-adherent adjuvant RT. It shows highly significant associations between RFS or OS and guideline adherent RT. Nevertheless, inadequate (R1-) surgical resection in a daily routine cohort of patients increases the risk of local recurrence and appears not to be compensated by the following RT.

Metastatic breast cancer: are we treating the same patients as in the past?

BACKGROUND: Early detection and improved (neo)-adjuvant treatment has extended survival of breast cancer over the last decades. It remains controversial whether a survival benefit is achieved once metastases have occurred. This study investigates survival trends in metastatic breast cancer (MBC) looking at the distribution of prognostic factors and the time period of the diagnosis of the primary and metastatic disease. PATIENTS AND METHODS: In this retrospective study, 1635 patients, diagnosed with MBC and treated at three German cancer centers, were included. For the survival analysis, patients were grouped into three time periods [1980-1994 (a), 1995-1999 (b) and 2000-2009 (c)], which were chosen according to the availability of new antineoplastic drugs for the treatment of MBC. Additionally, patients were divided into three risk groups using the simultaneously published prognostic score. RESULTS: The analysis of overall survival according to the date of primary diagnosis demonstrated a significant decline compared with the reference (a): (a versus b) hazard ratio (HR) = 1.37; P < 0.001; (a versus c) HR = 2.45; P < 0.001. Considering the time of first occurrence of metastasis, survival remains unchanged over the three periods (a versus b): HR = 0.94 P = 0.436; (a versus c): HR = 0.95; P = 0.435. However, a significant shift towards more unfavorable risk factors was seen. CONCLUSIONS: Although survival in MBC remains unchanged over time, patients developing metastatic disease have a more aggressive disease that is presumably compensated by more effective treatment. This alteration of tumor biology in MBC may be explained by a negative selection of patients with adverse risk profiles due to the advantages of the adjuvant therapy.

An internally and externally validated prognostic score for metastatic breast cancer: analysis of 2269 patients.

BACKGROUND: The prognosis of metastatic breast cancer (MBC) is extremely heterogeneous. Although patients with MBC will uniformly die to their disease, survival may range from a few months to several years. This underscores the importance of defining prognostic factors to develop risk-adopted treatment strategies. Our aim has been to use simple measures to judge a patient's prognosis when metastatic disease is diagnosed. PATIENTS AND METHODS: We retrospectively analyzed 2269 patients from four clinical cancer registries. The prognostic score was calculated from the regression coefficients found in the Cox regression analysis. Based on the score, patients were classified into high-, intermediate-, and low-risk groups. Bootstrapping and time-dependent receiver operating characteristic curves were used for internal validation. Two independent datasets were used for external validation. RESULTS: Metastatic-free interval, localization of metastases, and hormone receptor status were identified as significant prognostic factors in the multivariate analysis. The three prognostic groups showed highly significant differences regarding overall survival from the time of metastasis [intermediate compared with low risk: hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.36-2.27, P < 0.001; high compared with low risk: HR 3.54, 95% CI 2.81-4.45, P < 0.001). The median overall survival in these three groups were 61, 38, and 22 months, respectively. The external validation showed congruent results. CONCLUSIONS: We developed a prognostic score, based on routine parameters easily accessible in daily clinical care. Although major progress has been made, the optimal therapeutic management of the individual patient is still unknown. Besides elaborative molecular classification of tumors, simple clinical measures such as our model may be helpful to further individualize optimal breast cancer care.

Comparing the outcome between multicentric and multifocal breast cancer: what is the impact on survival, and is there a role for guideline-adherent adjuvant therapy? A retrospective multicenter cohort study of 8,935 patients.

Multifocal (MF) and multicentric (MC) breast cancers have been comprehensively studied, and their outcomes have been compared with unifocal (UF) tumors. We attempted to answer the following questions: (1) Does MF/MC presentation influence the outcome concerning BC mortality?, (2) Is there an impact of guideline-adherent adjuvant treatment in these BC subtypes?, and (3)What is the influence of guideline violations concerning surgery (breast-conserving surgery versus mastectomy) on the survival of MF/MC BC patients? Between 1992 and 2008, we retrospectively analyzed 8,935 breast cancer patients from 17 participating breast cancer centers within the BRENDA study group. Of 8,935 breast cancer patients, 7,073 (79.2 %) had UF tumors, 1,398 (15.6 %) had MF tumors, and 464 (5.2 %) had MC tumors. RFS was significantly worse for MF/MC BC patients compared to patients with UF tumors (MF p = 0.007; MC p = 0.019). OAS was significantly worse for MC patients but not for MF patients compared to patients with UF tumors (MF p = 0.321; MC p = 0.001). Guideline adherence was significantly lower in patients with MF (n = 580; 41.5 %) and MC (n = 204; 44.0 %) compared to patients with UF (n = 3,871; 54.7 %) (p < 0.001) tumors. Guideline violations were associated with a highly significant deterioration in survival throughout all subgroups except for MC, with respect to RFS and OAS. For 100 %-guideline-adherent patients, we could not find any significant differences in RFS and OAS after adjusting by nodal status, grade, and tumor size. Furthermore, we could not find any significant differences in RFS and OAS in patients with MF or MC stratified by breast-conserving therapy (BCT lumpectomy and radiation therapy) and mastectomy. There is a strong association between improved RFS and OAS in patients with MF/MZ BC. There are no significant differences in RFS and OAS for patients with breast-conserving therapy or mastectomy.

A comparison of international breast cancer guidelines - do the national guidelines differ in treatment recommendations?

AIM OF THE STUDY: Clinical practice guidelines (CPG) are an appropriate method to optimise routine clinical care. Numerous CPGs for the diagnosis and treatment of breast cancer have been developed by national health institutions or medical societies. While a comparison of methodological criteria has been undertaken before, it is unknown whether these CPGs differ in their actual treatment recommendations. METHODS: We included national breast cancer CPGs from the USA, Canada, Australia, the UK, and Germany that satisfy internationally recognised methodological criteria and are in widespread use in daily clinical care. Treatment recommendations for adjuvant invasive breast cancer including surgery, radiation, endocrine therapy, chemotherapy and anti-HER2-therapy were compared. RESULTS: Recommendations for endocrine therapy show discordances regarding optimal usage of ovarian function suppression for premenopausal patients and aromatase inhibitors for postmenopausal patients. However, most other treatment recommendations exhibit a large degree of congruency. This reflects the fact that they rest on the same evidence base, and that many national guidelines are adopted from other guidelines so that well accepted guidelines are cited within other guidelines. CONCLUDING STATEMENT: Considering that the development of guidelines is a very expensive and resource-intensive task the question arises whether the development of national guidelines in numerous countries is worth the effort since the recommendations differ only marginally.

Endocrine therapy in obese patients with primary breast cancer: another piece of evidence in an unfinished puzzle.

Obesity, defined as a body mass index (BMI) ≥30 is an independent risk factor in breast cancer and is correlated with shorter survival and enhanced recurrence rates. The present subgroup analysis of the German BRENDA-cohort aimed to investigate the correlation between BMI, recurrence-free survival (RFS) and adjuvant endocrine therapy. In this subgroup analysis, 4,636 patients were retrospectively examined using multivariate analyses. Overall 3,759 (81.1%) patients had a BMI <30 (non-obese) and 877 (18.9%) a BMI ≥30 (obese). In the group of all 3,896 (84.0%) patients with hormone-receptor-positive (HR+) breast carcinomas a significant reduction in RFS was demonstrated for those who were obese (P = 0.002; HR = 1.45 (95% CI: 1.15-1.83)), also after adjustment for Nottingham Prognostic Index (NPI) (P = 0.028; HR = 1.30 (95% CI: 1.03-1.65)). In hormone-receptor-negative (HR-) patients BMI had no influence on RFS (P = 0.380; HR = 1.20 (95% CI: 0.80-1.81)). Considering menopausal status, a significantly shorter RFS was seen in postmenopausal obese than in non-obese patients (P < 0.001; HR = 1.61 (95% CI: 1.24-2.09)), whereas the premenopausal patient group only showed a trend towards a shorter RFS (P = 0.202; HR = 1.44 (95% CI: 0.82-2.53)). The group of HR+ postmenopausal patients with normal or intermediate weight showed a non-significant statistical trend towards a survival benefit for aromatase inhibitors (AI) compared to tamoxifen (RFS: P = 0.486; HR = 1.29 (95% CI: 0.63-2.62), while obese patients tended to benefit more from tamoxifen (RFS: P = 0.289; HR = 0.65 (95% CI: 0.29-1.45)). In accordance with recently published results we demonstrated a negative effect of a high BMI on outcome in primary breast cancer. Furthermore the efficacy of AI seems dependent on BMI in contrast to tamoxifen. Prospective studies to optimise the therapy of obese breast cancer patients are urgently needed.

Triple-negative breast cancer: the impact of guideline-adherent adjuvant treatment on survival--a retrospective multi-centre cohort study.

Triple-negative breast cancer (TNBC) (ER-/PGR-/erb-2-) constitutes an aggressive subtype in breast cancer because it is accompanied by a significant decrease in overall survival (OAS) and recurrence-free survival (RFS) compared with hormone receptor positive breast cancers. This retrospective cohort study investigates the following issues: (1) Is there an impact of guideline-adherent treatment on RFS and OAS in TNBC? (2) Which adjuvant treatment has the most important impact on RFS and OAS in TNBC? This German retrospective multi-centre cohort study included 3,658 patients with primary breast cancer recruited from 2000 to 2005. The definition of guideline adherence was based on the German national S3 guideline for diagnosis and treatment of breast cancer (2004). A total of 371 patients (10.1%) had TNBC. Compared with HR+/erb-2- breast cancer (P = 0.001; HR = 1.75; 95% CI: 1.27-2.40), the recurrence rate of TNBC was significantly higher (P < 0.001; HR = 2.86; 95% CI: 2.17-3.76). Furthermore, the 5-year RFS and OAS was significantly lower in TNBC (RFS: 74.8% [95% CI: 68.8-80.8%] vs. 86.5% [95% CI: 84.6-88.4%] [log-rank P = 0.0001]) (OAS: 75.8% [95% CI: 69.9-81.8%] vs. 86.0% [95% CI: 84.1-87.9%] [log-rank P = 0.0001]). The most important parameters predicting RFS and OAS in TNBC after receiving guideline-conform chemotherapy are guideline-adherent surgery, radiotherapy, nodal status and grading. Overall, 66.8% TNBC were found with one or more (18%) guideline violations, which subsequently impaired OAS and RFS. The most important impact on OAS and RFS in TNBC patients was because of guideline violations (GV) concerning adjuvant radiotherapy and GV concerning adjuvant chemotherapy. Patients with TNBC primarily have a worse prognosis in terms of RFS and OAS than patients of a primarily non-TNBC phenotype. There is a strong association between guideline-adherent adjuvant treatment and improved survival outcome in TNBC. The outcome significantly decreases with the number of guideline violations.

Ultra-thin atomic layer deposited TiN films: non-linear I-V behaviour and the importance of surface passivation.

We report the electrical resistivity of atomic layer deposited TiN thin films in the thickness range 2.5-20 nm. The measurements were carried out using the circular transfer length method structures. For the films with thickness in the range of 10-20 nm, the measurements exhibited linear current-voltage (I-V) curves. The sheet resistance R(sh) was determined, and the resistivity was calculated. A value of 120 microohms-cm was obtained for a 20 nm TiN layer. With decreasing film thickness, the resistivity slightly increased and reached 135 microohms-cm for a 10 nm film. However, the measurements on 2.5-5.0 nm thick films revealed non-linear I-V characteristics, implying the dependence of the measured resistance, and therefore the resistivity, of the layers on applied voltage. The influence of the native oxidation due to the exposure of the films to air was taken into account. To fully eliminate this oxidation, a highly-resistive amorphous silicon layer was deposited directly after the ALD of TiN. The electrical measurements on the passivated 2.5- and 3.5 nm TiN layers then exhibited linear I-V characteristics. A resistivity of 400 and 310 microohms-cm was obtained for a 2.5- and 3.5 nm TiN film, respectively.

A difference in using atomic layer deposition or physical vapour deposition TiN as electrode material in metal-insulator-metal and metal-insulator-silicon capacitors.

In this work, metal-insulator-metal (MIM) and metal-insulator-silicon (MIS) capacitors are studied using titanium nitride (TiN) as the electrode material. The effect of structural defects on the electrical properties on MIS and MIM capacitors is studied for various electrode configurations. In the MIM capacitors the bottom electrode is a patterned 100 nm TiN layer (called BE type 1), deposited via sputtering, while MIS capacitors have a flat bottom electrode (called BE type 2-silicon substrate). A high quality 50-100 nm thick SiO2 layer, made by inductively-coupled plasma CVD at 150 degrees C, is deposited as a dielectric on top of both types of bottom electrodes. BE type 1 (MIM) capacitors have a varying from low to high concentration of structural defects in the SiO2 layer. BE type 2 (MIS) capacitors have a low concentration of structural defects and are used as a reference. Two sets of each capacitor design are fabricated with the TiN top electrode deposited either via physical vapour deposition (PVD, i.e., sputtering) or atomic layer deposition (ALD). The MIM and MIS capacitors are electrically characterized in terms of the leakage current at an electric field of 0.1 MV/cm (I leak) and for different structural defect concentrations. It is shown that the structural defects only show up in the electrical characteristics of BE type 1 capacitors with an ALD TiN-based top electrode. This is due to the excellent step coverage of the ALD process. This work clearly demonstrates the sensitivity to process-induced structural defects, when ALD is used as a step in process integration of conductors on insulation materials.

High estrogen receptor expression in early breast cancer: chemotherapy needed to improve RFS?

One of the most controversial questions in early breast cancer treatment is the need of chemotherapy in patients with estrogen receptor positive disease. Therefore, we analyzed a group of patients with high estrogen receptor (ER) expression to scrutinize the role of chemotherapy in this situation. To gauge the effect of chemotherapy on recurrence free survival (RFS) three treatment modalities were compared: endocrine treatment only, chemoendocrine treatment, and chemotherapy. 3,971 breast cancer patients whose treatment modalities as well as ER level were known, were included in this retrospective analysis. Their level of ER expression was documented as immunoreactive score (IRS). A high ER group was defined as ER IRS ≥ 9; primary endpoint was RFS. RFS was associated with ER, with the best outcome for strong and the worst result for negative expression. Adjusted to Nottingham prognostic index (NPI), RFS did not differ between the treatment cohorts of endocrine treatment and chemoendocrine treatment (P = 0.828) in the high ER group. Patients with chemotherapy alone fared significantly worse (P = 0.003). Even in high risk patients (according to NPI) the chemoendocrine and the endocrine treatment only groups did not differ significantly (HR = 1.15; 95% CI (0.56-2.34), P = 0.709). Omission of endocrine treatment led to significantly worse outcome (P = 0.013). In conclusion, RFS was significantly longer in patients with high ER expression than with weak or no ER expression. In the high expression group, there was no significant difference in RFS between endocrine treatment only and chemoendocrine therapy-even in high risk patients, for whom chemoendocrine treatment is routinely indicated. It seems insufficient for high ER patients to only consider tumor size, nodal status, and grading in order to decide which patient will benefit from adding chemotherapy to endocrine treatment.

[Summary of the practice guideline 'Lower urinary-tract symptoms in middle-aged and elderly men' (second revision) from the Dutch College of General Practitioners]. / Samenvatting van de standaard 'Bemoeilijkte mictie bij oudere mannen' (tweede herziening) van het Nederlands Huisartsen Genootschap.

The 1997 practice guideline from the Dutch College of General Practitioners concerning lower urinary-tract symptoms (LUTS) in middle-aged and elderly men has been revised and some points have been adapted. The underlying cause of LUTS in middle-aged and elderly men is an improperly functioning voiding mechanism of the bladder associated with ageing. Symptoms are not simply due to prostate enlargement. In uncomplicated LUTS the patient's perception of the level of inconvenience is very important in considering and choosing therapeutic options. Percussion of the bladder after micturition is no longer universally advised. In general, invasive treatment is more effective in relieving symptoms than medical treatment, although invasive treatment causes more adverse effects. LUTS and prostate cancer are different entities, and LUTS is not a risk factor for prostate cancer. The issue of prostate cancer is discussed in this practice guideline in order to clear up popular misconceptions and to enhance the practical implementation of this guideline.

Low-cost and nanoscale non-volatile memory concept for future silicon chips.

Non-volatile 'flash' memories are key components of integrated circuits because they retain their data when power is interrupted. Despite their great commercial success, the semiconductor industry is searching for alternative non-volatile memories with improved performance and better opportunities for scaling down the size of memory cells. Here we demonstrate the feasibility of a new semiconductor memory concept. The individual memory cell is based on a narrow line of phase-change material. By sending low-power current pulses through the line, the phase-change material can be programmed reversibly between two distinguishable resistive states on a timescale of nanoseconds. Reducing the dimensions of the phase-change line to the nanometre scale improves the performance in terms of speed and power consumption. These advantages are achieved by the use of a doped-SbTe phase-change material. The simplicity of the concept promises that integration into a logic complementary metal oxide semiconductor (CMOS) process flow might be possible with only a few additional lithographic steps.

Lower urinary tract symptoms: social influence is more important than symptoms in seeking medical care.

OBJECTIVE: To determine associations among lower urinary tract symptoms (LUTS), symptom severity, subjective beliefs and social influences when seeking primary medical care in men aged > or = 50 years. SUBJECTS AND METHODS: A population-based survey was conducted among 5052 men aged > or = 50 years, using patient registers of 22 general practitioners (GPs) in the Netherlands from November 1999 to May 2000. The questionnaire contained items concerning age, educational level, International Prostate Symptom Score (IPSS), bothersome score (BS), and questions from the Health Belief Model on attitude and social influences. The study population comprised men with an IPSS openface> 7. The odds ratios (ORs) corrected for the IPSS were calculated. RESULTS: In all, 3544 questionnaires (70.2%) were returned. Two groups of men with an IPSS openface> 7 were compared: those who consulted their GP in the previous 2 years because of voiding problems (268 cases) and the controls (272) who did not visit a GP for these symptoms. Cases more often thought a physician could improve their condition (OR 2.85), appeared to be more often advised by others to seek medical care (OR 6.36) and thought more often that this advice influenced their decision (OR 13.95). They also had more frequently received information from the media (OR 2.66) which affected their attendance (OR 12.52). In a multiple regression analysis, advice from others or information from the media were stronger predictors of seeking care than the influence of symptoms on daily life, the IPSS or the BS. CONCLUSION: Social influences, i.e. advice from others or the media, were more important factors in the decision to seek medical care than symptom severity.

Crime, disorder and legal pressure as a result of addiction problems in The Netherlands.

Coercing drug users into treatment might seem contrary to the philosophy of drug addiction care, which sets great store by the user's own motivation. Nevertheless, legal pressure and even force are increasingly being brought to bear in the Netherlands to persuade users to attend drug care programmes. The criminal justice system and the addiction care services have various means at their disposal to motivate addicts to come off drugs. This article discusses the relationship between addiction and crime. It begins with a brief description of how the addiction problem has evolved in the Netherlands over the years. This is followed by an explanation of how crime has developed during the same period and the effect this has had on social services for addicts. The article concludes with some recent policy proposals concerning diversion, coercion and pressurization strategies.

Rubidium transport in irradiated vitamin-E-deficient bone marrow cells.

We showed previously that the Rb+ transport rate in bone marrow cells (BMC) of vitamin-E-deficient mice is significantly lower than that in BMC of euvitaminotic mice. It is now evident that 4 h after whole-body, low-dose (0.01-1.0 Gy) gamma-irradiation of avitaminotic mice, there is an increase in the rate of Rb+ transport. This increase is quite pronounced, exceeding at all dose levels the rate of Rb+ transport in euvitaminotic mice exposed to the same radiation dose.

Determination of penicillin in pharmaceutical formulations by flow injection analysis using an optimised immobilised penicillinase reactor and iodometric detection.

An automated assay for the determination of penicillin in formulations suitable for use in pharmaceutical quality control is presented. The method is based on the classical iodometric penicillin assay which is incorporated in a flow injection analysis (FIA) system. The required hydrolysis is performed on-line by using an immobilised penicillinase reactor. Packed-bed and single-bead-string enzyme reactors are compared. It turns out that a packed-bed penicillinase reactor (10 cm x 1.5 mm i.d.) provides complete hydrolysis within short residence time, while only little back-pressure is generated. This enzyme reactor is stable for at least 9 months. Enzymatic hydrolysis of the beta-lactam ring results in the formation of the corresponding penicilloic acid, which consumes iodine. The iodine consumption is determined colorimetrically by measuring the decrease of the absorbance of the blue coloured iodine/starch complex. The optimum reactor length and flow rate for the colourimetrical detection reaction are determined. The optimised method is applied to the assay of penicillin in formulations and the results are compared with the "true" results obtained with a reference method: a mercurimetric titration. The reliability of the flow injection method is evaluated quantitatively by determining the maximum total error (MTE). The reliability is shown to be highest when measuring at a 0.3-mM level. Eight formulations including capsules, tablets and injectables containing penicillin G, amoxicillin or flucloxacillin are assayed. The MTE does not exceed the 6% level and the most probable MTE is between 1.5 and 3.5%.

Separation and identification of illicit heroin samples by liquid chromatography using an alumina and C18 coupled column system and photodiode array detection.

The analysis of illicit heroin and opium samples on a coupled alumina and C18 column system is described. The compounds to be analysed can be divided into two groups: those with low pKa values, such as caffeine, papaverine and noscapine, and those with high pKa values, such as heroin, acetylcodeine, O6-monoacetylmorphine, procaine, codeine, morphine and strychnine. The first group can best be separated on a C18 column, whereas alumina is more suitable for the second group. Previously reported criteria for choosing proper buffer systems for ion-exchange separations on alumina were used together with an iterative regressive optimization procedure developed in our laboratory. The system can be used with and without valve-switching, depending on the sample type. The peak purity of the judicially important components heroin and O6-monoacetylmorphine has been checked with a photodiode array detector and by use of advanced software.