Nontubal ectopic pregnancies: overview of diagnosis and treatment.

Nontubal ectopic pregnancies occur as a result of embryo implantation outside the uterine cavity and fallopian tubes. Sites include ovary, cervix, abdominal cavity, interstitial portion of fallopian tube, and cesarean scar. Nontubal pregnancies are uncommon. Nonspecific signs and symptoms of nontubal ectopic pregnancies make diagnosis challenging and, in many cases, significantly delayed, resulting in a high rate of morbidity. Although surgical management remains the mainstay of treatment, there is growing evidence that some of these can be managed medically or with the use of a combination of medical and surgical approaches with good outcome. This review summarizes the current diagnostic modalities, therapeutic options, and outcomes for nontubal ectopic pregnancies. Diagnostic and management options may be limited, especially in resource-restricted settings. Therefore, an understanding of the available options is critical. It needs to be emphasized that the rarity of cases and the difficulties in organizing ethically justified randomized trials result in the lack of well-established management guidelines for nontubal ectopic pregnancies.

Perspectives of Wisconsin Providers on Factors Influencing Receipt of Post-Mastectomy Breast Reconstruction.

BACKGROUND: The objective is to determine perspectives of general surgeons, plastic surgeons, and cancer navigators on factors contributing to breast cancer patients' decision for post-mastectomy reconstruction, especially for women facing financial hardship. METHODS: We mailed Wisconsin general and plastic surgeons who performed >5 breast cancer procedures annually a survey, including a postcard inviting cancer navigators to participate. Descriptive statistics summarize item responses. McNemar's chi-squared tests evaluated surgeons' perspectives of factors influencing reconstruction for all women compared to women facing financial hardship. RESULTS: Respondents include 70 general surgeons, 18 plastic surgeons, and 9 navigators. Respondents perceived preference-related factors as important, including "does not want more surgery" (85% reported it important overall and 77% for financial hardship women) and "reconstructed breast is not important to her" (77% vs. 61%). Surgeons perceived logistical factors were more important for women facing financial hardship, including "capacity to be away from work or home responsibilities for recovery" (30% reported important overall and 60% for financial hardship women), "concerned about out-of-pocket costs" (26% vs. 57%), and "frequent visits to complete reconstruction too burdensome" (27% vs. 49%). CONCLUSION: Our findings demonstrate Wisconsin surgeons and cancer navigators perceive logistical concerns influence reconstruction decisions for women facing financial hardship.

Rates of Ipsilateral Local-regional Recurrence in High-risk Patients Undergoing Immediate Post-mastectomy Reconstruction (AFT-01).

BACKGROUND: Some surgeons remain hesitant to perform immediate breast reconstruction (IBR) in patients with higher risk cancers owing to concerns about cancer recurrence and/or detection. Our objective was to determine the rate of ipsilateral local-regional recurrence for stage II/III patients who underwent IBR. METHODS: The National Cancer Database special study mechanism was used to create a stratified sample of women diagnosed with stage II/III breast cancer from 1217 facilities. Demographic, tumor, and recurrence data for women who underwent mastectomy with or without IBR were abstracted, including location of recurrence and method of detection. Estimates of 5-year local-regional recurrence rates were calculated and factors associated with recurrence were identified with multivariable Cox regression. RESULTS: Some 13% (692/5318) of stage II/III patients underwent IBR after mastectomy. Patients undergoing IBR were younger (P < .001), with fewer comorbid conditions (P < .001), and with lower tumor burden in the breast (P = .001) and the lymph nodes (P = 0.01). The 5-year rate of ipsilateral local-regional recurrence was 3.6% with no significant difference between patients with or without IBR (3.0% vs. 3.7%, P = .4). Most recurrences were detected by the patient (45%) or on physician examination (24%). Reconstruction was not associated with recurrence on multivariable analysis (hazard ratio = 0.83, P = .52). CONCLUSION: Women with stage II/III breast cancer selected for IBR had similar rates of ipsilateral local-regional recurrence compared with those undergoing mastectomy alone. Offering IBR after mastectomy in a patient-centered manner to select patients with stage II/III breast cancer is an acceptable consideration.

Systematic assessment of etiology in adults with a clinical diagnosis of young-onset type 2 diabetes is a successful strategy for identifying maturity-onset diabetes of the young.

OBJECTIVE: Misdiagnosis of maturity-onset diabetes of the young (MODY) remains widespread, despite the benefits of optimized management. This cross-sectional study examined diagnostic misclassification of MODY in subjects with clinically labeled young adult-onset type 1 and type 2 diabetes by extending genetic testing beyond current guidelines. RESEARCH DESIGN AND METHODS: Individuals were selected for diagnostic sequencing if they displayed features atypical for their diagnostic label. From 247 case subjects with clinically labeled type 1 diabetes, we sequenced hepatocyte nuclear factor 1 α (HNF1A) and hepatocyte nuclear factor 4 α (HNF4A) in 20 with residual ß-cell function ≥ 3 years from diagnosis (random or glucagon-stimulated C-peptide ≥ 0.2 nmol/L). From 322 with clinically labeled type 2 diabetes, we sequenced HNF1A and HNF4A in 80 with diabetes diagnosed ≤ 30 years and/or diabetes diagnosed ≤ 45 years without metabolic syndrome. We also sequenced the glucokinase (GCK) in 40 subjects with mild fasting hyperglycemia. RESULTS: In the type 1 diabetic group, two HNF1A mutations were found (0.8% prevalence). In type 2 diabetic subjects, 10 HNF1A, two HNF4A, and one GCK mutation were identified (4.0%). Only 47% of MODY case subjects identified met current guidelines for diagnostic sequencing. Follow-up revealed a further 12 mutation carriers among relatives. Twenty-seven percent of newly identified MODY subjects changed treatment, all with improved glycemic control (HbA(1c) 8.8 vs. 7.3% at 3 months; P = 0.02). CONCLUSIONS: The systematic use of widened diagnostic testing criteria doubled the numbers of MODY case subjects identified compared with current clinical practice. The yield was greatest in young adult-onset type 2 diabetes. We recommend that all patients diagnosed before age 30 and with presence of C-peptide at 3 years' duration are considered for molecular diagnostic analysis.

Safety of antipsychotics in people with intellectual disability.

BACKGROUND: Despite frequent use, little is known about the metabolic and endocrine side-effects of antipsychotics in individuals with intellectual disability. AIMS: To compare indices of obesity, glucose, lipids and prolactin between antipsychotic-treated and antipsychotic-naive individuals with intellectual disability and also between participants with intellectual disability and controls from the general population. METHOD: Observational study comparing 138 antipsychotic-treated and 64 antipsychotic-naive participants with intellectual disability in one National Health Service trust with general population controls. RESULTS: Antipsychotic treatment comprised: risperidone 48%,olanzapine 18%, thioxanthenes 10%, other 24%; monotherapy 95% of participants; mean treatment duration 8 years;median daily chlorpromazine equivalent dose 108 mg(range 16­667). Metabolic indices were the same or more favourable in the intellectual disability group than the general population control group but overweight/obesity and type 2 diabetes were more prevalent in the women in the intellectual disability group than the control group. Metabolic indices were similar, statistically or clinically, between the antipsychotic-treated and the antipsychotic-naive groups but there was a non-significant trend towards a higher rate of type 2 diabetes in the antipsychotic group. A total of 100%and 70% of participants on amisulpride/sulpiride and risperidone respectively had hyperprolactinaemia, with secondary hypogonadism in 77% and 4% of affected women and men. CONCLUSIONS: Antipsychotics, on average, did not increase metabolic risk,although the existence of a susceptible subgroup at risk of diabetes cannot be excluded. Some antipsychotics induced hyperprolactinaemic hypogonadism, requiring active management. However, our findings suggest that antipsychotics at the low doses routinely prescribed for people with intellectual disability are generally safe in relation to metabolic adverse effects, even if efficacy remains poorly defined.

Evaluation of serum 1,5 anhydroglucitol levels as a clinical test to differentiate subtypes of diabetes.

OBJECTIVE: Assignment of the correct molecular diagnosis in diabetes is necessary for informed decisions regarding treatment and prognosis. Better clinical markers would facilitate discrimination and prioritization for genetic testing between diabetes subtypes. Serum 1,5 anhydroglucitol (1,5AG) levels were reported to differentiate maturity-onset diabetes of the young due to HNF1A mutations (HNF1A-MODY) from type 2 diabetes, but this requires further validation. We evaluated serum 1,5AG in a range of diabetes subtypes as an adjunct for defining diabetes etiology. RESEARCH DESIGN AND METHODS: 1,5AG was measured in U.K. subjects with: HNF1A-MODY (n = 23), MODY due to glucokinase mutations (GCK-MODY, n = 23), type 1 diabetes (n = 29), latent autoimmune diabetes in adults (LADA, n = 42), and type 2 diabetes (n = 206). Receiver operating characteristic curve analysis was performed to assess discriminative accuracy of 1,5AG for diabetes etiology. RESULTS: Mean (SD range) 1,5AG levels were: GCK-MODY 13.06 microg/ml (5.74-29.74), HNF1A-MODY 4.23 microg/ml (2.12-8.44), type 1 diabetes 3.09 microg/ml (1.45-6.57), LADA 3.46 microg/ml (1.42-8.45), and type 2 diabetes 5.43 (2.12-13.23). Levels in GCK-MODY were higher than in other groups (P < 10(-4) vs. each group). HNF1A-MODY subjects showed no difference in unadjusted 1,5AG levels from type 2 diabetes, type 1 diabetes, and LADA. Adjusting for A1C revealed a difference between HNF1A-MODY and type 2 diabetes (P = 0.001). The discriminative accuracy of unadjusted 1,5AG levels was 0.79 for GCK-MODY versus type 2 diabetes and 0.86 for GCK-MODY versus HNF1A-MODY but was only 0.60 for HNF1A-MODY versus type 2 diabetes. CONCLUSIONS: In our dataset, serum 1,5AG performed well in discriminating GCK-MODY from other diabetes subtypes, particularly HNF1A-MODY. Measurement of 1,5AG levels could inform decisions regarding MODY diagnostic testing.

Perceptions of heart attack risk amongst individuals with diabetes.

AIM: Individuals with diabetes are at increased risk of cardiovascular disease (CVD). There is good evidence that this risk can be reduced by pharmacotherapies and lifestyle modification. Despite this, knowledge of CVD risk amongst individuals with diabetes remains poor. We undertook a qualitative study to investigate lay perceptions of heart attack risk amongst individuals with diabetes in order to gather information about underlying perceptions concerning risk and risk reduction strategies. METHODS: We conducted three focus groups in Oxford using an open-ended question map. Content analysis was performed to identify recurring themes, similar patterns, distinctions and supportive quotations. RESULTS: Concern about having a heart attack varied widely. A commonly held view was that a 10-year heart attack risk of 10% or greater was high and being aware of one's risk was important so that lifestyle changes or other interventions could be implemented. Participants consistently viewed physical activity as potentially harmful. Almost all participants sought healthcare and lifestyle advice from their primary healthcare providers in the first instance, preferring this to information in the lay press or government campaigns. CONCLUSION: The focus groups have allowed us to better understand lay perceptions of, and underlying assumptions about, CVD risk. These findings may be of use when discussing CVD risk and risk reduction strategies in primary care.

Use of focus groups to develop methods to communicate cardiovascular disease risk and potential for risk reduction to people with type 2 diabetes.

BACKGROUND: People need to perceive a risk in order to build an intention-to-change behaviour yet our ability to interpret information about risk is highly variable. OBJECTIVES: We aimed to use a user-centred design process to develop an animated interface for the UK Prospective Diabetes Study (UKPDS) Risk Engine to illustrate cardiovascular disease (CVD) risk and the potential to reduce this risk. In addition, we sought to use the same approach to develop a brief lifestyle advice intervention. METHODS: Three focus groups were held. Participants were provided with examples of materials used to communicate CVD risk and a leaflet containing a draft brief lifestyle advice intervention and considered their potential to increase motivation-to-change behaviours including diet, physical activity, and smoking in order to reduce CVD risk. Discussions were tape-recorded, transcribed and coded and recurring themes sought. RESULTS: Sixty-two percent of participants were male, mean age was 66 years (range = 47-76 years) and median age at leaving full-time education was 18 years (range = 15-40 years). Sixteen had type 2 diabetes and none had a prior history of CVD. Recurring themes from focus group discussions included the following: being less numerate is common, CVD risk reduction is important and a clear visual representation aids comprehension. CONCLUSION: A simple animated interface of the UKPDS Risk Engine to illustrate CVD risk and the potential for reducing this risk has been developed for use as a motivational tool, along with a brief lifestyle advice intervention. Future work will investigate whether use of this interactive version of the UKPDS Risk Engine and brief lifestyle advice is associated with increased behavioural intentions and changes in health behaviours designed to reduce CVD risk.

A real-time, mobile phone-based telemedicine system to support young adults with type 1 diabetes.

Telemedicine systems have been proposed as a means of supporting people with diabetes in the self-management of their condition. Requirements for monitoring parameters of care, including glycaemic control, extent of analysis and interpretation of data, patient-clinician contacts, and involvement of a multidisciplinary care team with effective communication, can be addressed by telemedicine systems. We describe the development and implementation of an innovative real-time telemedicine system based around transmission and feedback of data to and from a mobile phone. Proprietary Java-based programs were used to link a blood glucose meter to a mobile phone. In addition to immediate transmission of blood glucose data, information about insulin dose, eating patterns and physical exercise were collected. Immediate feedback to the phone included a colour histogram to draw attention to levels of control over glycaemia over the previous two weeks. Clinicians supporting patients had access to summary screens identifying users not testing, and those with levels of blood glucose outside pre-defined limits. More detailed graphical displays of data were used to provide data about control of insulin dose and the degree to which it was modified in response to diet and exercise. The system has been evaluated in a clinical trial conducted in secondary care and is now being adapted for use in a trial in primary care, which is designed to assess its effectiveness in providing integrated management for the patient, general practitioner and pharmacist.

A randomized controlled trial of the effect of real-time telemedicine support on glycemic control in young adults with type 1 diabetes (ISRCTN 46889446).

OBJECTIVE: To determine whether a system of telemedicine support can improve glycemic control in type 1 diabetes. RESEARCH DESIGN AND METHODS: A 9-month randomized trial compared glucose self-monitoring real-time result transmission and feedback of results for the previous 24 h in the control group with real-time graphical phone-based feedback for the previous 2 weeks together with nurse-initiated support using a web-based graphical analysis of glucose self-monitoring results in the intervention group. All patients aged 18-30 years with HbA(1c) (A1C) levels of 8-11% were eligible for inclusion. RESULTS: A total of 93 patients (55 men) with mean diabetes duration (means +/- SD) 12.1 +/- 6.7 years were recruited from a young adult clinic. In total, the intervention and control groups transmitted 29,765 and 21,400 results, respectively. The corresponding median blood glucose levels were 8.9 mmol/l (interquartile range 5.4-13.5) and 10.3 mmol/l (6.5-14.4) (P < 0.0001). There was a reduction in A1C in the intervention group after 9 months from 9.2 +/- 1.1 to 8.6 +/- 1.4% (difference 0.6% [95% CI 0.3-1.0]) and a reduction in A1C in the control group from 9.3 +/- 1.5 to 8.9 +/- 1.4% (difference 0.4% [0.03-0.7]). This difference in change in A1C between groups was not statistically significant (0.2% [-0.2 to 0.7, P = 0.3). CONCLUSIONS: Real-time telemedicine transmission and feedback of information about blood glucose results with nurse support is feasible and acceptable to patients, but to significantly improve glycemic control, access to real-time decision support for medication dosing and changes in diet and exercise may be required.