Schizophrenia and attendance in primary healthcare: a population-based matched cohort study.

Objective: Schizophrenia is associated with high mortality, somatic comorbidity and reduced life expectancy. The general practitioner (GP) plays a key role in the treatment of mental and physical multimorbidity. Nevertheless, it is unclear how much individuals with schizophrenia use primary healthcare. This study aims to investigate the yearly numbers of consultations in general practice for individuals with schizophrenia. Design and Setting: We performed a population-based matched cohort study of 21,757 individuals with schizophrenia and 435,140 age- and gender-matched references from Danish National Registers. Monthly general practice consultations were analysed using a generalized linear model with log link and assuming negative binomial distribution. Main outcome measures: Consultation rates in general practice up to17 years after index diagnosis. Results: Individuals with schizophrenia attended their GP more than references throughout the study period. The cases had 82% (95% CI: 78-87) and 76% (95% CI: 71-80) more consultations in primary care after 1 year and 5 years, respectively. Individuals with both schizophrenia and comorbid somatic illness attended even more. Conclusion: Individuals with schizophrenia are in regular contact with their GP, especially if they have comorbid illnesses. Whether an average of six consultations per year for individuals with schizophrenia is sufficient is up for debate. The study demonstrates a potential for an increased prevention and treatment of individuals with schizophrenia in general practice. KEY POINTS Schizophrenia is associated with high mortality, somatic comorbidity and reduced life expectancy. Little is known about the attendance pattern in primary care for individuals with schizophrenia. •We found high attendance rates in primary care for individuals diagnosed with schizophrenia from index diagnosis and at least 17 years after diagnosis, which suggests opportunities for earlier intervention to improve their somatic health. •We found an association between high illness comorbidity and increased risk of not attending the general practitioner. The most severely somatically and mentally ill individuals may thus be difficult to reach and support in the current healthcare system.

Bereavement, multimorbidity and mortality: a population-based study using bereavement as an indicator of mental stress.

BACKGROUND: Mental stress is associated with higher mortality, but it remains controversial whether the association is causal or a consequence of a higher physical disease burden in those with a high mental stress load. Understanding causality is important when developing targeted interventions. We aimed to estimate the effect of mental stress on mortality by performing a 'natural' experiment using spousal bereavement as a disease-independent mental stressor. METHODS: We followed a population-based matched cohort, including all individuals in Denmark bereaved in 1997-2014, for 17 years. Prospectively recorded register data were obtained for civil and vital status, 39 mental and physical diagnoses, and socioeconomic factors. RESULTS: In total, 389 316 bereaved individuals were identified and 137 247 died during follow-up. Bereaved individuals had higher all-cause mortality than non-bereaved references in the entire study period. The relative mortality in the bereaved individuals was highest shortly after the loss (adjusted hazard ratio (aHR), first month: 2.50, 95% confidence interval (CI) 2.37-2.63; aHR, 6-12 months: 1.38, 95% CI 1.34-1.42). The excess mortality rate associated with bereavement rose with increasing number of physical diseases (1.33 v. 7.00 excess death per 1000 person-months for individuals with 0 v. ⩾3 physical conditions during the first month) and was exacerbated by the presence of mental illness. The excess mortality among bereaved individuals was primarily due to death from natural causes. CONCLUSIONS: Bereavement was associated with increased short-term and long-term mortality, even after adjustment for morbidities, which suggests that mental stress may play a causal role in excess mortality.

Increased use of primary care during 6 years of prodromal schizophrenia.

BACKGROUND: Early diagnosis is important for the course of schizophrenia. AIM: To investigate whether prodromal symptoms of schizophrenia lead to increased use of primary care. METHOD: A register-based cohort study of 21 894 cases with incident schizophrenia and 437 880 matched controls. RESULTS: Cases used daytime primary care 43% more than controls during the 6 years before diagnosis (IRR = 1.43; 95% CI: 1.39; 1.48) and 132% more during the last 2 months (IRR = 2.32; 95% CI: 2.27; 2.37), and 34% (IRR = 1.34; 95% CI: 1.23; 1.48) vs. 374% more for out-of-hours services (IRR = 3.74; 95% CI: 3.52; 3.98). Six years before index diagnosis, 30% of cases had at least one psychiatric contact without being diagnosed with schizophrenia, increasing to 75% 1 month before diagnosis. CONCLUSION: Increased help-seeking behaviour was seen at least 6 years before index diagnosis, suggesting a 'window' for earlier diagnosis of prodromal schizophrenia.

Euroforgen-NoE collaborative exercise on LRmix to demonstrate standardization of the interpretation of complex DNA profiles.

There has been very little work published on the variation of reporting practices of mixtures between laboratories, but it has been previously demonstrated that there is little consistency. This is because there is no current uniformity of practice, so different laboratories will operate using different rules. The interpretation of mixtures is not solely a matter of using some software to provide 'an answer'. An assessment of a case will usually begin with a consideration of the circumstances of a crime. Assumptions made about the numbers of contributors follow from an examination of the electropherogram(s)--and these may differ between the prosecution and the defence hypotheses. There may be a necessity to evaluate several sets of hypotheses for any given case if the circumstances are uncertain. Once the hypotheses are formulated, the mathematical analysis is complex and can only be accomplished by the use of specialist software. In order to obtain meaningful results, it is essential that scientists are trained, not only in the use of the software, but also in the methodology to understand the likelihood ratio concept that is used. The Euroforgen-NoE initiative has developed a training course that utilizes the LRmix program to carry out the calculations. This software encompasses the recommendations of the ISFG DNA commissions on mixture interpretation and is able to interpret samples that may come from two or more contributors and may also be partial profiles. Recently, eighteen different laboratories were trained in the methodology. Afterwards they were asked to independently analyze two different cases with partial mixture DNA evidence and to write a statement court-report. We show that by introducing a structured training programme, it is possible to demonstrate, for the first time, that a high degree of standardization, leading to uniformity of results can be achieved by participating laboratories.

Secondary cancers, comorbidities and mortality associated with nitrogen mustard therapy in patients with mycosis fungoides: a 30-year population-based cohort study.

BACKGROUND: Topical nitrogen mustard is a widely used therapy in patients with mycosis fungoides (MF). However, it remains controversial whether nitrogen mustard therapy is associated with increased risk of secondary cancers and chronic pulmonary diseases in patients with MF. OBJECTIVES: To assess the risk of secondary cancers, comorbidities, mortality and cause-specific mortality in patients with MF treated with nitrogen mustard compared with patients not receiving this treatment. METHODS: Linking the Danish nationwide registries in a 30-year population-based cohort study, we compared 110 patients with MF from a regional Danish centre using nitrogen mustard treatment with 193 patients from Danish centres not using nitrogen mustard. The two cohorts were compared by Cox regression analysis. RESULTS: Overall, secondary cancers were not significantly increased [hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.46-1.56], and subanalyses showed no significantly increased risk of nonmelanoma skin cancers, malignant melanomas or cancers in the respiratory organs in the nitrogen mustard-treated cohort. Furthermore, we found no significantly increased risk of any category of comorbidity, including chronic pulmonary diseases, in patients treated with nitrogen mustard (HR 0.93, 95% CI 0.48-1.81). Moreover, mortality and cause-specific mortality did not significantly differ between the two cohorts. CONCLUSIONS: This study does not support any previous suspicion of increased risk of secondary cancers and chronic pulmonary diseases among patients with MF treated with nitrogen mustard. Furthermore, mortality and cause-specific mortality were not influenced by nitrogen mustard treatment. Thus our findings indicate that topical nitrogen mustard is a safe therapy in patients with MF.

Distance to screening site and non-participation in screening for breast cancer: a population-based study.

BACKGROUND: In population-based breast cancer screening programmes, the geographical distance to the screening site may influence a woman's propensity to participate. The aim of this study was to analyse the effect driving distance to the screening unit had on women's participation in a breast cancer screening programme. METHODS: All women invited to the first round of breast cancer screening in the Central Denmark Region were eligible for inclusion (n = 149,234). Information on participation was collected from a regional administrative database. The shortest road distance between each woman's residence and her affiliated screening site was assessed using Network Analyst, ArcGIS. RESULTS: The unadjusted association between distance and non-participation formed a J-shape curve. Adjustment for socio-demographic characteristics caused the J-shape to disappear, and the probability of non-attendance rose with longer distance to the screening site but flattened after ~45 km. Women without access to a vehicle had a higher risk of non-participation than women with access to a vehicle. CONCLUSIONS: A long road distance to the screening site was associated with an increased risk of non-participation. Women without access to a vehicle were at higher risk of non-participation than women who had access to a vehicle.

Topical nitrogen mustard therapy in patients with mycosis fungoides or parapsoriasis.

BACKGROUND: Topical nitrogen mustard is a chemotherapeutic agent used in treatment of mycosis fungoides (MF). OBJECTIVE: To evaluate the response and side effects in patients with MF and parapsoriasis treated with topical nitrogen mustard. METHODS: A retrospective study of treatment response in 116 patients diagnosed with MF and 71 patients with parapsoriasis and treated with topical nitrogen mustard from 1991 to 2009. RESULTS: Overall response rate and complete response (CR) rate was 91.4% and 53.4% in patients with MF and 90.1% and 40.8% in patients with parapsoriasis, respectively. Relapse following CR was observed in 67.7% in patients with MF and 62.1% in patients with parapsoriasis. Freedom-from-relapse was higher in patients with T1-T2 than in T3 disease (P < 0.01). Progressive disease (PD) occurred in 25.0% and 26.8% in patients with MF and parapsoriasis, respectively. Progression-free survival was similar in patients with T1-T2 compared with T3 (P = 0.79) and T4 disease (P = 0.22) and lower in patients with parapsoriasis with <10% than >10% skin involvement (P = 0.05). CONCLUSION: The present study confirms that topical nitrogen mustard is a safe and effective therapy. The treatment response in patients with parapsoriasis was not statistically different from the response in patients with MF. This supports, that parapsoriasis is not a distinct entity, but an early stage of MF. Nitrogen mustard should therefore still be considered as an important treatment modality in patients with early stages (parapsoriasis) and later stages of MF either as monotherapy or in combination with other topical or systemic therapies.

Satiety scores and satiety hormone response after sucrose-sweetened soft drink compared with isocaloric semi-skimmed milk and with non-caloric soft drink: a controlled trial.

BACKGROUND/OBJECTIVES: Observational studies indicate that sugar-sweetened soft drinks (SSSD) may promote obesity, among other factors, owing to low-satiating effects. The effect of energy in drinks on appetite is still unclear. We examined the effect of two isocaloric, but macronutrient, different beverages (SSSD versus semi-skimmed milk) and two non-energy-containing beverages (aspartame-sweetened soft drink (ASSD) and water) on appetite, appetite-regulating hormones and energy intake (EI). SUBJECTS/METHODS: In all, 24 obese individuals were included in a crossover trial. Each subject was served either 500 ml of SSSD (regular cola: 900 kJ), semi-skimmed milk (950 kJ), ASSD (diet cola: 7.5 kJ), or water. Subjective appetite scores, ghrelin, GLP-1, and GIP concentrations were measured at baseline and continuously 4-h post intake. Ad libitum EI was measured 4 h after intake of the test drinks. RESULTS: Milk induced greater subjective fullness and less hunger than regular cola (P<0.05). Also, milk led to 31% higher GLP-1 (95% CI: 20, 44; P<0.01) and 45% higher GIP (95% CI: 23, 72; P<0.01) concentrations compared with SSSD. Ghrelin was equally 20% lower after milk and SSSD compared with water. The total EI (ad libitum EI+EI from the drink) was higher after the energy-containing drinks compared with diet cola and water (P<0.01). CONCLUSIONS: Milk increased appetite scores and GLP-1 and GIP responses compared with SSSD. The energy containing beverages were not compensated by decreased EI at the following meal, emphasizing the risk of generating a positive energy balance by consuming energy containing beverages. Furthermore, there were no indications of ASSD increased appetite or EI compared with water.

Topical nitrogen mustard therapy in patients with Langerhans cell histiocytosis.

BACKGROUND: Langerhans cell histiocytosis (LCH) is characterized by abnormal proliferation and infiltration of Langerhans cells in different organs. The skin is frequently involved either as unisystem or multisystem disease. OBJECTIVES: To review the clinical response and side-effects of nitrogen mustard therapy in LCH in children and adults with unisystem or multisystem disease. PATIENTS AND METHODS: This retrospective study includes 10 children and four adults with LCH, treated with nitrogen mustard from 1975 to 2010. The median extent of skin involvement was 46% (range 5-100%). RESULTS: Overall, 13 patients had complete or partial response. Although eight patients achieved a complete response with a median time of 12·3months (range 36 days to 1·9 years), six of these patients ultimately relapsed. One patient, who had unisystem disease limited to the skin, initially showed progression of her cutaneous lesions with nitrogen mustard treatment. Although subsequently the cutaneous lesions completely regressed, concomitant systemic involvement was noted. Four other patients similarly experienced improvement of their skin lesions with treatment, but also exhibited progression of the LCH systemically. The patients were treated with other therapies prior and adjunctive to nitrogen mustard. However, five patients had progression to other organs, despite regression of skin lesions, which supports that the treatment effect in the skin is related to topical nitrogen mustard. Six patients developed contact dermatitis to nitrogen mustard. CONCLUSIONS: Topical nitrogen mustard can be an effective and safe therapy in both children and adults with cutaneous LCH, although relapses are common.

Postgraduate multidisciplinary development program: impact on the interpretation of pelvic MRI in patients with rectal cancer: a clinical audit in West Denmark.

BACKGROUND: Pelvic MRI in patients with rectal cancer is an accepted tool for the identification of patients with poor prognostic tumors who may benefit from neoadjuvant therapy. In Denmark, this examination has been mandatory in the workup on rectal cancer since 2002. OBJECTIVE: This study aimed to assess the impact of a multidisciplinary team course for doctors in West Denmark on the technical quality, reporting, and interpretation of pelvic MRI in rectal cancer. DESIGN: This study is interventional and observational. Two expert reviewers served as reference standard in the evaluation of consecutively performed pelvic MRI scans against which the evaluations from the participating centers were compared. SETTINGS: Five imaging centers in West Denmark performed pelvic MRI in rectal cancer from March 1 to December 31, 2007. PATIENTS: One hundred and eighty patients with newly diagnosed rectal cancer were enrolled. INTERVENTIONS: This study involved a multidisciplinary team course including on-site visits. MAIN OUTCOME MEASURES: The MR scans were evaluated concerning technical performance, reporting, interpretation, and the ability to correctly allocate patients to chemoirradiation based on imaging findings pre- and postcourse. RESULTS: Eighteen percent of the scans were of satisfying technical quality for staging rectal cancer before the course compared with 74% after (P < .001). After the course, the T-stage subclassification, the depth of extramural spread, the N stage, and the presence of extramural vascular invasion was reported significantly more frequently. Based on imaging findings, we observed no significant effect on the ability to perform correct treatment stratification according to Danish guidelines. LIMITATIONS: The evaluation process itself may have improved the performance of the participating centers. CONCLUSIONS: Performance and reporting of pelvic MRI in patients with rectal cancer can be improved significantly through multidisciplinary development courses and on-site visits, whereas improvements in image interpretation with regard to treatment stratification may demand more intensive efforts.