Iatrogenic opioid use disorder, chronic pain and psychiatric comorbidity: A systematic review.

OBJECTIVE: A systematic review of the literature on the risks of developing iatrogenic opioid use disorders in chronic pain patients with psychiatric comorbidity. METHODS: We conducted literature searches on Pubmed with key subjects: "chronic pain", "psychiatry", "opioids" and "opioid use disorder" and for original, English written articles published from 2000 until the first of September 2017. Final selection of the articles for review was made in a consensus between three reviewers. RESULTS: Longitudinal studies showed a significant association between psychiatric comorbidity, especially depression and anxiety disorders and the development of problematic opioid use, more severe opioid craving and poor opioid treatment outcome (analgesia and side effects) in chronic pain patients. Cross-sectional studies showed a similar association between psychiatric disorders and problematic opioid use, where studies in specialized pain settings showed a higher prevalence of psychiatric disorders, compared to non-specialized settings. CONCLUSIONS: This systematic review showed a significant association between psychiatric comorbidity, especially depression and anxiety disorders and the development of problematic opioid use in chronic pain patients. We therefore recommend psychiatric screening in chronic pain management. Chronic pain patients with comorbid psychiatric disorders need a multidisciplinary approach and monitoring opioid use is warranted in these patients.

Spinal cord stimulation in experimental chronic painful diabetic polyneuropathy: Delayed effect of High-frequency stimulation.

BACKGROUND: Spinal cord stimulation (SCS) has been shown to provide pain relief in painful diabetic polyneuropathy (PDPN). As the vasculature system plays a great role in the pathophysiology of PDPN, a potential beneficial side-effect of SCS is peripheral vasodilation, with high frequency (HF) SCS in particular. We hypothesize that HF-SCS (500 Hz), compared with conventional (CON) or low frequency (LF)-SCS will result in increased alleviation of mechanical hypersensitivity in chronic experimental PDPN. METHODS: Diabetes was induced in 8-week-old female Sprague-Dawley rats with an intraperitoneal injection of 65 mg/kg of streptozotocin (n = 44). Rats with a significant decrease in mechanical withdrawal response to von Frey filaments over a period of 20 weeks were implanted with SCS electrodes (n = 18). Rats were assigned to a cross-over design with a random order of LF-, CON-, HF- and sham SCS and mechanical withdrawal thresholds were assessed with von Frey testing. RESULTS: Compared with sham treatment, the average 50% WT score for 5 Hz was 4.88 g higher during stimulation (p = 0.156), and 1.77 g higher post-stimulation (p = 0.008). CON-SCS resulted in 50% WT scores 5.7 g, and 2.51 g higher during (p = 0.064) and after stimulation (p < 0.004), respectively. HF-SCS started out with an average difference in 50% WT score compared with sham of 1.87 g during stimulation (p = 0.279), and subsequently the steepest rise to a difference of 5.47 g post-stimulation (p < 0.001). CONCLUSIONS: We demonstrated a delayed effect of HF-SCS on mechanical hypersensitivity in chronic PDPN animals compared with LF-, or CON-SCS. SIGNIFICANCE: This study evaluates the effect of SCS frequency (5-500 Hz) on mechanical hypersensitivity in the chronic phase of experimental PDPN. High frequency (500 Hz) - SCS resulted in a delayed effect- on pain-related behavioural outcome in chronic PDPN.

Bilateral ECT induces bilateral increases in regional cortical thickness.

Electroconvulsive therapy (ECT) is the most effective treatment for patients suffering from severe or treatment-resistant major depressive disorder (MDD). Unfortunately its underlying neurobiological mechanisms are still unclear. One line of evidence indicates that the seizures produced by ECT induce or stimulate neuroplasticity effects. Although these seizures also affect the cortex, the effect of ECT on cortical thickness is not investigated until now. We acquired structural magnetic resonance imaging data in 19 treatment-resistant MDD patients before and after a bilateral ECT course, and 16 healthy controls at 2 time points, and compared changes in cortical thickness between the groups. Our results reveal that ECT induces significant, bilateral increases in cortical thickness, including the temporal pole, inferior and middle temporal cortex and the insula. The pattern of increased cortical thickness was predominant in regions that are associated with seizure onset in ECT. Post hoc analyses showed that the increase in thickness of the insular cortex was larger in responders than in non-responders, which may point to a specific relationship of this region with treatment effects of ECT.

Assessment of disease activity in patients with rheumatoid arthritis using optical spectral transmission measurements, a non-invasive imaging technique.

OBJECTIVES: In rheumatoid arthritis (RA), treat-to-target strategies require instruments for valid detection of joint inflammation. Therefore, imaging modalities are increasingly used in clinical practice. Optical spectral transmission (OST) measurements are non-invasive and fast and may therefore have benefits over existing imaging modalities. We tested whether OST could measure disease activity validly in patients with RA. METHODS: In 59 patients with RA and 10 patients with arthralgia, OST, joint counts, Disease Activity Score (DAS) 28 and ultrasonography (US) were performed. Additionally, MRI was performed in patients with DAS28<2.6. We developed and validated within the same cohort an algorithm for detection of joint inflammation by OST with US as reference. RESULTS: At the joint level, OST and US performed similarly inproximal interphalangeal-joints (area under the receiver-operating curve (AUC) of 0.79, p<0.0001) andmetacarpophalangeal joints (AUC 0.78, p<0.0001). Performance was less similar in wrists (AUC 0.62, p=0.006). On the patient level, OST correlated moderately with clinical examination (DAS28 r=0.42, p=0.001), and US scores (r=0.64, p<0.0001). Furthermore, in patients with subclinical and low disease activity, there was a correlation between OST and MRI synovitis score (RAMRIS (Rheumatoid Arthritis MRI Scoring) synovitis), r=0.52, p=0.005. CONCLUSIONS: In this pilot study, OST performed moderately in the detection of joint inflammation in patients with RA. Further studies are needed to determine the diagnostic performance in a new cohort of patients with RA.

Familial liability for metoprolol-induced psychosis.

OBJECTIVE: Beta-blockers are commonly used in the treatment of hypertension and cardiac arrhythmias. The incidence of neuropsychiatric side effects is generally low. This case report shows the potential familial liability of a metoprolol-induced psychosis. METHOD: We report a case of metoprolol-induced psychosis. Potential pharmocogenetic factors mediating this familial metoprolol-induced psychosis are discussed. RESULTS: A middle-aged man developed psychosis after starting metoprolol, which diminished after ceasing the medication. Two of his family members experienced similar symptoms after using metoprolol. All family members were genotyped as CYP2D6*4 allele carriers indicating reduced CYP2D6 enzyme activity. CONCLUSION: The case presented here suggests a potential familial liability for metoprolol- induced psychosis. Pharmacokinetic mechanisms are hypothesized to mediate this familial liability through genetic variation in the CYP2D6 genotype. A family history of psychotic symptoms after treatment with beta-blockers should be taken into account, when prescribing this beta-blocker.

Trends in breast biopsies for abnormalities detected at screening mammography: a population-based study in the Netherlands.

BACKGROUND: Diagnostic surgical breast biopsies have several disadvantages, therefore, they should be used with hesitation. We determined time trends in types of breast biopsies for the workup of abnormalities detected at screening mammography. We also examined diagnostic delays. METHODS: In a Dutch breast cancer screening region 6230 women were referred for an abnormal screening mammogram between 1 January 1997 and 1 January 2011. During two year follow-up clinical data, breast imaging-, biopsy-, surgery- and pathology-reports were collected of these women. Furthermore, breast cancers diagnosed >3 months after referral (delays) were examined, this included review of mammograms and pathology specimens to determine the cause of the delays. RESULTS: In 41.1% (1997-1998) and in 44.8% (2009-2010) of referred women imaging was sufficient for making the diagnosis (P<0.0001). Fine-needle aspiration cytology decreased from 12.7% (1997-1998) to 4.7% (2009-2010) (P<0.0001), percutaneous core-needle biopsies (CBs) increased from 8.0 to 49.1% (P<0.0001) and surgical biopsies decreased from 37.8 to 1.4% (P<0.0001). Delays in breast cancer diagnosis decreased from 6.7 to 1.8% (P=0.003). CONCLUSION: The use of diagnostic surgical breast biopsies has decreased substantially. They have mostly been replaced by percutaneous CBs and this replacement did not result in an increase of diagnostic delays.

A brief cognitive-behavioral intervention for treating depression and panic disorder in patients with noncardiac chest pain: a 24-week randomized controlled trial.

BACKGROUND: Most patients with noncardiac chest pain experience anxiety and depressive symptoms. Commonly they are reassured and referred back to primary care, leaving them undiagnosed and untreated. Some small studies have suggested efficacy of 12 cognitive behavioral therapy (CBT) sessions. Our aim was to examine efficacy of brief CBT in reducing anxiety and depressive symptoms in patients with noncardiac chest pain and comorbid panic and/or depressive disorders. METHODS: In this 24-week randomized controlled trial comparing CBT (n = 60) versus treatment as usual (TAU, n = 53), we included all adults who presented at the cardiac emergency unit of a university hospital with noncardiac chest pain, scored ≥8 on the hospital anxiety and depression scale (HADS) and were diagnosed with a comorbid panic and/or depressive disorder with the Mini International Neuropsychiatric Interview. CBT consisted of six individual sessions. Main outcome was disease severity assessed with the clinical global inventory (CGI) by a blinded independent rater. RESULTS: ANCOVA in the intention-to-treat and completer sample showed that CBT was superior to TAU after 24 weeks in reducing disease severity assessed with CGI (P < .001). Secondary outcomes on anxiety (HADS-anxiety, state trait anxiety inventory (STAI)-trait) and depressive symptoms (Hamilton depression rating scale) were in line with these results except for HADS-depression (P = .10), fear questionnaire (P = .13), and STAI-state (P = .11). CONCLUSIONS: Brief CBT significantly reduces anxiety and depressive symptoms in patients with noncardiac chest pain who are diagnosed with panic and/or depressive disorders. Patients presenting with noncardiac chest pain should be screened for psychopathology and if positive, CBT should be considered.

The cardiac anxiety questionnaire: cross-validation among cardiac inpatients.

OBJECTIVE: General anxiety symptoms are common in patients with cardiac disease and considered to have an adverse effect on cardiac prognosis. The role of specific cardiac anxiety, however, is still unknown. The aim of this study is to examine the factor structure, reliability, and validity of the Dutch version of the Cardiac Anxiety Questionnaire (CAQ), which was specifically designed to assess heart focused anxiety. METHODS: Two hundred thirty-seven patients admitted for an acute coronary syndrome (ACS) and a control group of 49 patients admitted for an exacerbation of rheumatoid arthritis (RA) completed the CAQ, the Agoraphobic Cognitions Questionnaire, Mobility Inventory, Beck Depression Inventory, Beck Anxiety Inventory, and the State-Trait Anxiety Inventory. RESULTS: Although the original three-factor solution (fear, avoidance, and attention) was acceptable (model fit parameters: CFI = 0.89 and TLI = 0.87), our data were best explained by a four-factor model including safety seeking behaviors. Internal consistency and test-retest reliability were good. The CAQ had moderate correlations with the other anxiety and depression questionnaires. Recently admitted ACS patients had significantly higher scores than RA patients, even after controlling for general anxiety and depressive symptoms (p < 0.001). CONCLUSION: The CAQ is a reliable and valid instrument to assess cardiac anxiety in patients hospitalized with ACS. These results enable longitudinal studies to examine the relationship of heart-focused anxiety with cardiac prognosis and to evaluate interventions specifically targeted at anxiety in cardiac patients.

One-year follow up of cardiac anxiety after a myocardial infarction: a latent class analysis.

INTRODUCTION: Longitudinal elevated depressive symptom scores are associated with a less favorable cardiac outcome. Although anxiety has received less attention, meta-analysis suggests that high baseline levels of general anxiety might worsen cardiac outcome. The objective of this study was to explore the longitudinal course of cardiac anxiety after a myocardial infarction (MI). METHODS: The Cardiac Anxiety Questionnaire (CAQ) was administered to 194 patients hospitalized for MI after admission, and one, three, six and twelve months after discharge. Latent class growth analysis (LCGA) was performed to identify groups based on cardiac anxiety course. Between group differences were checked on relevant socio-demographic, cardiac and psychiatric variables. RESULTS: LCGA identified three groups with stable CAQ levels over time, indicative of high (7.7%), intermediate (45.4%) and low (30.4%) levels of cardiac anxiety, respectively. A fourth group (16.5%) reported high levels of cardiac anxiety that decreased over time. Between group differences were of particular interest for the two subgroups that started high in cardiac anxiety, since these may differentiate patients with spontaneous remission from those who might be in need of treatment. Patients in whom cardiac anxiety persisted were less often employed, had more diabetes mellitus, a history of acute coronary syndrome, depressive symptoms, anxiety and avoidance at baseline and a lower quality of life at follow-up. CONCLUSION: This first study addressing cardiac anxiety after an MI identified four trajectories. Future studies should focus on cardiac outcome and treatment strategies for cardiac anxiety in the subgroup with persistent high anxiety levels.

Value of Memorial Sloan-Kettering Cancer Center nomogram in clinical decision making for sentinel lymph node-positive breast cancer.

BACKGROUND: The aim of this study was to determine the value of the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram for individual decision making in a Dutch cohort of women with breast cancer with a positive sentinel lymph node (SLN) but at low risk of additional nodal metastases. METHODS: Data were collected on 168 patients with a positive SLN who underwent completion axillary lymph node dissection. The predicted probability of non-SLN metastases was calculated for each patient, using the MSKCC nomogram. Specificity and false-negative rates were calculated for subgroups with a predicted risk of no more than 5, 10 or 15 per cent. A receiver operating characteristic (ROC) curve was constructed and the area under the curve (AUC) calculated. RESULTS: The discrimination of the MSKCC nomogram, measured by the AUC, was 0.68. For low predicted probability cut-off values of no more than 5, 10 and 15 per cent, the false-negative rates were 20, 14 and 19 per cent, and the specificities were 4, 27 and 32 per cent, respectively. The low-risk category (5 per cent or less) consisted of only 3.0 per cent of the study population. CONCLUSION: The performance of the MSKCC nomogram was insufficient to make it a useful tool for individual decision making in this cohort of women with SLN-positive breast cancer.

Localization of non-palpable breast cancer using a radiolabelled titanium seed.

BACKGROUND: Resection guided by a radiologically placed hookwire is the most common surgical technique for non-palpable breast cancer. This technique has several well described disadvantages such as incidental migration, kinking or fracture of the wire, and difficult logistics between the radiology, surgical and nuclear medicine departments. Use of an iodine-125-radiolabelled (I-125) seed for localization of non-palpable breast tumours could potentially prevent these problems. METHODS: Data on use of the I-125 seed localization technique in 325 consecutive women were collected prospectively between October 2003 and June 2009. All patients with screen-detected, histologically proven malignancy were included. Patients with a preoperative core biopsy showing either ductal carcinoma in situ or unclear pathology were excluded from this study. RESULTS: The mean(s.d.) age of the women was 59.5(11.9) years. Localization was guided ultrasonographically in 275 procedures, stereotactically in 45 and by both techniques in five. The I-125 seed was removed by surgery after a mean of 4(5) days. The mean duration of operation was 62.9(21.2) min. Complete tumour removal was achieved in 310 procedures (95.4 per cent). CONCLUSION: Localization of impalpable breast cancer using a I-125 seed was safe and led to a high proportion of radical lumpectomies.

Primary squamous cell carcinoma of the thyroid years after radioactive iodine treatment.

Primary squamous cell carcinoma (SCC) of the thyroid gland is a rare diagnosis, since there is no squamous epithelium in the thyroid gland. SCC of the thyroid is highly aggressive with a poor prognosis. We present a case of primary SCC of the thyroid: this 88-year-old male patient had a history of hyperthyroidism which was treated with radioactive iodine 25 years earlier. Whether this treatment could be related to SCC of the thyroid is not clear. We treated our patient with thyroidectomy and subsequent intensified radiotherapy. Six months after treatment our patient is doing well and there is no sign of local reoccurrence. Our work-up is described, including the differentiation from metastatic disease. The origin of squamous cell carcinoma in the thyroid is uncertain; we discuss some theoretical considerations. We conclude that after excluding metastatic disease, thyroidectomy combined with radiotherapy is the treatment of choice.

[Acute abdominal pain and fever in a young woman as the first symptoms of lymphangioleiomyomatosis]. / Acute buikpijn en koorts bij een jonge vrouw als eerste verschijnselen van lymfangioleiomyomatose.

A previously healthy 28-year-old woman presented to the emergency clinic with acute severe abdominal pain and high fever. A diagnostic laparoscopy was performed, during which a large retroperitoneal tumour was found. A CT-scan of the abdomen and thorax confirmed the presence of a retroperitoneal mass but also revealed multiple renal angiomyolipomas and extensive cystic lesions in all lung fields. Based on these findings, the diagnosis lymphangioleiomyomatosis (LAM) was suspected, and later confirmed by histological examination of a biopsy specimen. The acute abdomen and fever appeared to have been caused by a Streptococcus agalactiae infection of the retroperitoneal lymphangiomyoma, which was treated with intravenous antibiotics. LAM is a very rare disease affecting mostly women of childbearing age and presenting almost exclusively with pulmonary symptoms. This is the first description of LAM presenting with an acute surgical abdomen and fever due to infection of a lymphangiomyoma.

Reviewing the structural features of autologous platelet-leukocyte gel and suggestions for use in surgery.

The therapeutic use of autologously prepared platelet-leukocyte gel (PLG) is a relatively new technology which might stimulate and accelerate soft-tissue and bone healing. The effectiveness of this procedure lies in the exogenous delivery of a wide range of platelet growth factors, intentionally released from autologously prepared PLG. The rationale to employ this technique is to mimic physiological wound healing and reparative tissue processes. Despite an increase in clinical PLG applications, the structures and kinetics of this biological material have not been completely examined. Electron microscopic imaging was performed to evaluate platelet-leukocyte gel structures. Furthermore, directions for PLG application are presented, based on results from published articles in various surgical disciplines. In conclusion, PLG can be useful in a wide range of clinical applications to enhance healing following surgical procedures, since exogenous applied PLG releases instantly platelet growth factors, in the presence of leukocytic cells.

Margin status and the risk of local recurrence after breast-conserving treatment of lobular breast cancer.

BACKGROUND: Invasive lobular breast carcinoma is known for its multicentricity and is associated with a higher incidence of incomplete excision after breast-conserving therapy. The aim of the study was to examine the influence of positive surgical margins on the local recurrence rate in patients diagnosed with invasive lobular cancer and treated with breast-conserving therapy. METHODS: All 416 women diagnosed with invasive lobular breast cancer and undergoing breast-conserving treatment between 1995 and 2002 were selected from the population-based Eindhoven Cancer Registry. Their medical charts were reviewed and detailed information was collected. RESULTS: The risk of margin involvement was 29% after the first operation and 17% when taking into account the final margin status of the patients undergoing re-excision. During follow-up, 18 patients developed a local recurrence. The 5 year actuarial risk of developing a local recurrence was 3.5% (95% confidence interval 2.5-4.5) and the 8 year risk was 6.4% (95% confidence interval 4.7-8.0). There was no influence of positive surgical margins on the risk of local recurrence, neither in the univariate analysis nor after adjustment for age, tumour size, nodal status and adjuvant systemic treatment. CONCLUSION: Patients with invasive lobular cancer, treated with breast-conservation, have a low risk of local recurrence, despite their high risk of having a microscopically incomplete excision of the tumour.

The significance of one positive axillary node.

AIMS: The aim of this study was to identify a subgroup of patients with breast cancer that can safely avoid axillary dissection. METHODS: Using data collected by the Eindhoven Cancer Registry, we compared the clinico-pathological features of 489 patients with only one positive lymph node to those of 817 patients with more than one positive lymph node in the axilla. All patients underwent complete axillary dissection, not preceded by a sentinel node biopsy. RESULTS: Tumour size greater than 1cm, harvesting more than 15 axillary lymph nodes at histopathological examination, metastasis size larger than 2mm, extranodal extension, and nodal involvement of the axillary apex are independently associated with the occurrence of more than one metastatic axillary lymph node. CONCLUSION: No subgroup could be identified in which axillary dissection can always be omitted. However, tumour size<1cm, finding a micrometastasis rather than a macrometastasis, and especially not finding extranodal extension were independently associated with finding only one positive axillary lymph node.

Long-term survival of T1 and T2 lymph node-negative breast cancer patients according to Mitotic Activity Index: a population-based study.

Node-negative breast cancer patients have a relatively good prognosis, but eventually one-third will die of the disease. Thus, prognostic factors to identify the high-risk group among these patients are needed. We retrospectively determined the Mitotic Activity Index (MAI) for a large series of node-negative breast cancer patients (n = 468) with tumours smaller than 5 cm, who only received locoregional treatment. Patients were followed for up to 29 years; crude and relative survival were calculated, both univariate and multivariate. Relative survival differed significantly according to MAI (p = 0.05), the difference occurred in the first 5 years after diagnosis and remained constant thereafter. After adjustment, MAI still significantly affected relative survival (RER, 1.9; 95% CI, 1.1-3.5). Tumour size also increased the risk, but this was not statistically significant (RER, 1.5; 95% CI, 0.8-2.7). Survival of patients with a T1 tumour and MAI < 10 was similar to that for the general population in the first 5 years after diagnosis. In conclusion, MAI significantly predicted long-term survival for T1/T2N0 breast cancer. Adjuvant systemic therapy appears to have little benefit for node-negative breast cancer patients with a T1 tumour, regardless of the MAI. For those with a T2 tumour and a MAI > or = 10 systemic therapy might have reduced mortality. The need for close surveillance of node-negative breast cancer patients with a T1 tumour and MAI < 10 seems limited.

The prognostic significance of axillary lymph-node micrometastases in breast cancer patients.

AIMS: We analysed the results of regional community practice to determine the prognosis of axillary lymph-node micrometastases in women with breast cancer. METHODS: Patient data were retrieved from the population-based Eindhoven Cancer Registry in The Netherlands. Between 1975 and 1997, 10,111 patients were diagnosed as having invasive breast cancer. We compared three subgroups: patients without axillary involvement (the pN0 group), patients with axillary micrometastasis (< or = 2 mm, the pN1a group), and patients with a macro metastasis in only one lymph node (> 2 mm, the pN1 group). Follow-up was completed until April 2002. RESULTS: The relative risk (RR) of dying comparing the pN1a group and the pN1 group to the pN0 group was 1.32 and 1.34, respectively. Excluding the adjuvantly treated patients, the RR of dying was 1.51 and 1.91, respectively for the pN1a group and the pN1 group vs. the pN0 group. CONCLUSION: This outcome data of nearly 25 years of community practice show that breast cancer patients with axillary lymph node micrometastasis have a significantly worse survival rate than those without independent of age or tumour size. Adjuvant systemic therapy should be contemplated when treating these patients.

Inelastic state-to-state scattering of OH (2Pi3/2, J=3/2,f) by HCl.

Parity resolved state-to-state cross sections for inelastic scattering of OH (X2Pi) by HCl were measured in a crossed molecular beam experiment at the collision energy of 920 cm(-1). The OH (X2Pi) radicals were prepared in a single quantum state, Omega=3/2, J=3/2, MJ=3/2, f, by means of electrostatic state selection in a hexapole field. The rotational distribution of the scattered OH radicals by HCl was probed by saturated LIF spectroscopy of the 0-0 band of the A 2Sigma+ - X 2Pi transition. Relative state-to-state cross sections were measured for rotational excitations up to J=9/2 within the Omega=3/2 spin-orbit manifold and up to J=7/2 within the Omega=1/2 spin-orbit manifold. A propensity for spin-orbit conserving transitions was found, but no propensity for excitation into a particular Lambda-doublet component of the same rotational state was evident. The data are presented and discussed in comparison with results previously obtained for collisions of OH with CO (Ecoll=450 cm(-1)) and N2 (Ecoll=410 cm(-1)) and with new data we have measured for the OH+CO system at a comparable collision energy (Ecoll=985 cm(-1)). This comparison suggests that the potential energy surface (PES) governing the interaction between OH and HCl is more anisotropic than the PES's governing the intermolecular interaction of OH with CO and N2.

Mammography screening in the Netherlands: delay in the diagnosis of breast cancer after breast cancer screening.

In a prospective study we determined the frequency and causes of delay in the diagnosis of breast cancer after suspicious screening mammography. We included all women aged 50-75 years who underwent biennial screening mammography in the southern breast cancer screening region of the Netherlands between 1 January 1996 and 1 January 2002. Clinical data, breast imaging reports, biopsy results and breast surgery reports were collected of all women with a positive screening result with a minimum of 2-year follow-up. Of 153 969 mammographic screening examinations, 1615 (1.05%) were positive screens. Breast cancer was diagnosed in 770 (47.9%) of 1607 women for whom follow-up information was available, yielding a cancer detection rate of 5.0 per 1000 women screened. Breast cancer was diagnosed within 3 months following a positive screen in 722 cases (93.8%). The diagnostic delay was 4-6, 7-12 and 13-24 months, respectively, in 11 (1.4%), 24 (3.1%) and nine (1.2%) patients. In four other patients (0.5%), breast cancer was diagnosed after a repeat positive screen, resulting in a diagnostic delay of 25-27 months. Reasons for a diagnostic delay >3 months were erroneous mammographic interpretation of suspicious lesions as benign or probably benign lesions (33 cases), benign biopsies from a malignant lesion (10), and omission to biopsy or remove a lesion that was suspicious at breast imaging (4) or core biopsy (1). We conclude that there is room for improvement in the workup of patients with a positive screening mammography, as seen from data in this screening region. To improve the workup, we suggest that other breast cancer screening programmes also identify delay in breast cancer diagnosis after a positive screen.