- Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose.
- To provide updated, practical guidelines for the pathologic diagnosis of MM.
- Pathologists involved in the ...International Mesothelioma Interest Group and others with an interest and expertise in the field contributed to this update. Reference material included up-to-date, peer-reviewed publications and textbooks.
- There was discussion and consensus opinion regarding guidelines for (1) distinguishing benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) recognition of the key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiating epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid MM, (7) use of molecular markers in the diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels employed is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Depending on the morphology, immunohistochemical panels should contain both positive and negative markers for mesothelial differentiation and for lesions considered in the differential diagnosis. Immunohistochemical markers should have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic and membranous markers). Selected molecular markers are now being used to distinguish benign from malignant mesothelial proliferations. These guidelines are meant to be a practical diagnostic reference for the pathologist; however, some new pathologic predictors of prognosis and response to therapy are also included.
Introduction: The rural and remote nature of many First Nations communities in Northwestern Ontario, Canada poses unique obstacles to physically accessing health care, in addition to other barriers. ...Indigenous peoples face similar challenges globally. First Nations communities experience significant health inequities, including cancer burden, which can be attributed to complex factors associated with colonization and Westernization. One potentially promising intervention to decrease the burden of advanced cancers is the provision of accessible, convenient and culturally sensitive cancer screening services, leading to early detection and treatment. The Wequedong Lodge Cancer Screening Program (WLCSP) was a pilot project aiming to provide cancer screening education and opportunistic cancer screening to residents from rural and remote First Nations communities while accessing health services in the urban center of Thunder Bay, Ontario, Canada.
Methods: Cancer screening education and opportunistic breast, cervical and colorectal cancer screening appointments were offered to individuals and their travel escorts already staying at Wequedong Lodge. Program uptake was determined primarily by education participation, and secondarily by client participation in screening.
Results: In total, the WLCSP booked 1033 appointments, with 841 being attended. Over the program's 3 years there was an increase in clients each year. Specifically, 22% (60/275) of age-eligible women completed a mammogram. Pap tests were provided to 8% (45/554) of age-eligible females. Finally, 32% (106/333) of all age-eligible service participants were given a fecal occult blood test kit. An evaluation survey (n=396) demonstrated overall client satisfaction with the program.
Conclusion: The WLCSP aimed to provide education about, access to and uptake of cancer screening services for First Nations people from rural and remote communities in Northwestern Ontario by targeting inequalities in accessing cancer screening opportunities. Therefore, program uptake may provide helpful numerical comparisons for similar future programs globally. Other entities working to improve cancer screening rates in remote and/or rural populations and/or amongst Indigenous peoples may find consideration of the WLCSP processes, successes and challenges helpful to their efforts.
Hereditary spastic paraplegias (HSP) are a rare heterogeneous group of inherited neurodegenerative diseases characterized by progressive lower extremity spasticity and weakness. Mutations of the ...kinesin family member 5A (KIF5A) gene lead to a spectrum of phenotypes ranging from spastic paraplegia type 10 to Charcot-Marie Tooth Disease type 2. We report the second known case of a mutation in the KIF5A gene at c.610C>T presenting with HSP plus an axonal sensorimotor neuropathy.
The obesity epidemic has major public health consequences. Expert dietetic and behavioural counselling with intensive follow-up is effective, but resource requirements severely restrict widespread ...implementation in primary care, where most patients are managed. We aimed to estimate the effectiveness and cost-effectiveness of an internet-based behavioural intervention (POWeR+) combined with brief practice nurse support in primary care.
We did this pragmatic, parallel-group, randomised controlled trial at 56 primary care practices in central and south England. Eligible adults aged 18 years or older with a BMI of 30 kg/m2 or more (or ≥28 kg/m2 with hypertension, hypercholesterolaemia, or diabetes) registered online with POWeR+—a 24 session, web-based, weight management intervention lasting 6 months. After registration, the website automatically randomly assigned patients (1:1:1), via computer-generated random numbers, to receive evidence-based dietetic advice to swap foods for similar, but healthier, choices and increase fruit and vegetable intake, in addition to 6 monthly nurse follow-up (control group); web-based intervention and face-to-face nurse support (POWeR+Face-to-face POWeR+F; up to seven nurse contacts over 6 months); or web-based intervention and remote nurse support (POWeR+Remote POWeR+R; up to five emails or brief phone calls over 6 months). Participants and investigators were masked to group allocation at the point of randomisation; masking of participants was not possible after randomisation. The primary outcome was weight loss averaged over 12 months. We did a secondary analysis of weight to measure maintenance of 5% weight loss at months 6 and 12. We modelled the cost-effectiveness of each intervention. We did analysis by intention to treat, with multiple imputation for missing data. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN21244703.
Between Jan 30, 2013, and March 20, 2014, 818 participants were randomly assigned to the control group (n=279), the POWeR+F group (n=269), or the POWeR+R group (n=270). Weight loss averaged over 12 months was recorded in 666 (81%) participants. The control group lost almost 3 kg over 12 months (crude mean weight: baseline 104·38 kg SD 21·11; n=279, 6 months 101·91 kg 19·35; n=136, 12 months 101·74 kg 19·57; n=227). The primary imputed analysis showed that compared with the control group, patients in the POWeR+F group achieved an additional weight reduction of 1·5 kg (95% CI 0·6–2·4; p=0·001) averaged over 12 months, and patients in the POWeR+R group achieved an additional 1·3 kg (0·34–2·2; p=0·007). 21% of patients in the control group had maintained a clinically important 5% weight reduction at month 12, compared with 29% of patients in the POWeR+F group (risk ratio 1·56, 0·96–2·51; p=0·070) and 32% of patients in the POWeR+R group (1·82, 1·31–2·74; p=0·004). The incremental overall cost to the health service per kg weight lost with the POWeR+ interventions versus the control strategy was £18 (95% CI −129 to 195) for POWeR+F and –£25 (−268 to 157) for POWeR+R; the probability of being cost-effective at a threshold of £100 per kg lost was 88% and 98%, respectively. No adverse events were reported.
Weight loss can be maintained in some individuals by use of novel written material with occasional brief nurse follow-up. However, more people can maintain clinically important weight reductions with a web-based behavioural program and brief remote follow-up, with no increase in health service costs. Future research should assess the extent to which clinically important weight loss can be maintained beyond 1 year.
Health Technology Assessment Programme of the National Institute for Health Research.
In their contribution to the AJIL Symposium, Robinson and MacNeil remark that a prolific legacy of the International Criminal Tribunal for Yugoslavia (ICTY) and the International Criminal Tribunal ...for Rwanda (ICTR) is that “it is now commonsense that rape is and must be a war crime.” This line distills the complexity of the legacies of the tribunals regarding sexual and gender-based violence. On the one hand, it articulates the critical role of the tribunals in cementing the idea that sexual violence, hitherto largely relegated to indifference in international criminal law and policy frameworks, is worthy of international attention. Simultaneously, it encapsulates the ways in which the tribunals’ jurisprudence has been received globally to narrate a narrow conception of conflict-related sexual violence as a “weapon of war” or committed as part of “strategic” conflict-related goals. In fact, there is little that constitutes common sense about sexual violence in conflict, nor is it always, or even most predominantly, committed as a war crime, crime against humanity,or in pursuit of genocide as envisaged by international criminal law. Various studies suggest that sexual violence in war takes many forms and causalities with differentiation across and within conflict contexts.
Objective: The aim of this pilot project was to investigate how Nurse Practitioners (NP) manage medical service delivery gaps in a socio-disadvantaged rural Victorian region.
Design: A ...cross-sectional study utilising data from patient consultations that took place at the Nurse Practitioner Community Clinic (NPCC) over six months in 2013 and patient satisfaction survey.
Setting: The NPCC is a rural clinic servicing a rural population in Victoria.
Subjects: 629 patients.
Main outcome measures: Numbers of patients; presentations; age; gender; postcode; reason for encounter; consultation length; availability of General Practitioner (GP); consultation activities and follow up; NP Medicare Benefits Scheme (MBS) item number rebate; and equivalent GP MBS item number rebates.
Results: Over 50% of patients were female; 60% aged over 45 years. Patients had 2.6 encounters with the NPCC; over 50% lasting between 10 and 20 minutes. Approximately half the revenue of that claimed in equivalent GP encounters. Common reasons for attendance were symptoms and complaints (37.2%) and attendance was viewed as convenient and accessible, despite having a regular GP (47.8%). Fifty six Patients responded to a satisfaction survey and indicated they were satisfied with the service would use the service again and would recommend it.
Conclusions: The NPCC provided an accessible service that met patients' needs in a rural community. The study provides evidence that NPs can provide medical management in areas where medical service delivery gaps exist. However, there was a significant discrepancy between funding reimbursements for services provided at the NPCC and those provided by GPs.
Behavioural counselling with intensive follow-up for obesity is effective, but in resource-constrained primary care settings briefer approaches are needed.
To estimate the clinical effectiveness and ...cost-effectiveness of an internet-based behavioural intervention with regular face-to-face or remote support in primary care, compared with brief advice.
Individually randomised three-arm parallel trial with health economic evaluation and nested qualitative interviews.
Primary care general practices in the UK.
Patients with a body mass index of ≥ 30 kg/m
(or ≥ 28 kg/m
with risk factors) identified from general practice records, recruited by postal invitation.
Positive Online Weight Reduction (POWeR+) is a 24-session, web-based weight management intervention completed over 6 months. Following online registration, the website randomly allocated participants using computer-generated random numbers to (1) the control intervention (
= 279), which had previously been demonstrated to be clinically effective (brief web-based information that minimised pressure to cut down foods, instead encouraging swaps to healthier choices and increasing fruit and vegetables, plus 6-monthly nurse weighing); (2) POWeR+F (
= 269), POWeR+ supplemented by face-to-face nurse support (up to seven contacts); or (3) POWeR+R (
= 270), POWeR+ supplemented by remote nurse support (up to five e-mails or brief telephone calls).
The primary outcome was a modelled estimate of average weight reduction over 12 months, assessed blind to group where possible, using multiple imputation for missing data. The secondary outcome was the number of participants maintaining a 5% weight reduction at 12 months.
A total of 818 eligible individuals were randomised using computer-generated random numbers. Weight change, averaged over 12 months, was documented in 666 out of 818 participants (81%; control,
= 227; POWeR+F,
= 221; POWeR+R,
= 218). The control group maintained nearly 3 kg of weight loss per person (mean weight per person: baseline, 104.4 kg; 6 months, 101.9 kg; 12 months, 101.7 kg). Compared with the control group, the estimated additional weight reduction with POWeR+F was 1.5 kg 95% confidence interval (CI) 0.6 to 2.4 kg;
= 0.001 and with POWeR+R was 1.3 kg (95% CI 0.34 to 2.2 kg;
= 0.007). By 12 months the mean weight loss was not statistically significantly different between groups, but 20.8% of control participants, 29.2% of POWeR+F participants (risk ratio 1.56, 95% CI 0.96 to 2.51;
= 0.070) and 32.4% of POWeR+R participants (risk ratio 1.82, 95% CI 1.31 to 2.74;
= 0.004) maintained a clinically significant 5% weight reduction. The POWeR+R group had fewer individuals who reported doing another activity to help lose weight control, 47.1% (64/136); POWeR+F, 37.2% (51/137); POWeR+R, 26.7% (40/150). The incremental cost to the health service per kilogram weight lost, compared with the control group, was £18 (95% CI -£129 to £195) for POWeR+F and -£25 (95% CI -£268 to £157) for POWeR+R. The probability of being cost-effective at a threshold of £100 per kilogram was 88% and 98% for POWeR+F and POWeR+R, respectively. POWeR+R was dominant compared with the control group. No harms were reported and participants using POWeR+ felt more enabled in managing their weight. The qualitative studies documented that POWeR+ was viewed positively by patients and that health-care professionals generally enjoyed supporting patients using POWeR+.
Maintenance of weight loss after 1 year is unknown.
Identifying strategies for longer-term engagement, impact in community settings and increasing physical activity.
Clinically valuable weight loss (> 5%) is maintained in 20% of individuals using novel written materials with brief follow-up. A web-based behavioural programme and brief support results in greater mean weight loss and 10% more participants maintain valuable weight loss; it achieves greater enablement and fewer participants undertaking other weight-loss activities; and it is likely to be cost-effective.
Current Controlled Trials ISRCTN21244703.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in
; Vol. 21, No. 4. See the NIHR Journals Library website for further project information.
Hearing in noise is a challenge for all listeners, especially for those with hearing loss. This study compares cues used for detection of a low-frequency tone in noise by older listeners with and ...without hearing loss to those of younger listeners with normal hearing. Performance varies significantly across different reproducible, or “frozen,” masker waveforms. Analysis of these waveforms allows identification of the cues that are used for detection. This study included diotic (N
0
S
0
) and dichotic (N
0
S
π
) detection of a 500-Hz tone, with either narrowband or wideband masker waveforms. Both diotic and dichotic detection patterns (hit and false alarm rates) across the ensembles of noise maskers were predicted by envelope-slope cues, and diotic results were also predicted by energy cues. The relative importance of energy and envelope cues for diotic detection was explored with a roving-level paradigm that made energy cues unreliable. Most older listeners with normal hearing or mild hearing loss depended on envelope-related temporal cues, even for this low-frequency target. As hearing threshold at 500 Hz increased, the cues for diotic detection transitioned from envelope to energy cues. Diotic detection patterns for young listeners with normal hearing are best predicted by a model that combines temporal- and energy-related cues; in contrast, combining cues did not improve predictions for older listeners with or without hearing loss. Dichotic detection results for all groups of listeners were best predicted by interaural envelope cues, which significantly outperformed the classic cues based on interaural time and level differences or their optimal combination.
There is evidence to suggest that repeated alcohol detoxifications have an adverse cognitive impact. The Abstinence Preparation Group (APG) intervention is based on Cognitive Behaviour Therapy (CBT) ...and is aiming to help people who developed dependence on alcohol to regain control over their drinking, initiate lifestyle changes, and enhance self-efficacy. The current project aimed to explore the theoretical mechanism of APG: whether self-efficacy, urges to drink, positive expectancies, and negative expectancies from drinking are changing during therapy, whether these changes are consistent with expectancy and social learning theory predictions, and whether they are correlated with reduction of drinking.
Methods: Clients were assessed at baseline before starting APG (t0), immediately after completion of APG (t1), and at 1 month post detoxification from alcohol (t2).
Results: Thirty-five participants were recruited. APG has reduced symptoms of dependence during the period of intervention and at follow-up. Key concepts have changed significantly both during the intervention and at follow-up, with the exception of negative expectances. All of the above-mentioned changes were consistent with theory prediction.
Discussion: The findings improve our understanding of the important components of the APG. This is the only intervention aiming to reduce the adverse cognitive impact of alcohol detoxification.
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