Retaining dermatology patients in primary care through dialogue with secondary care providers: A service evaluation.

BACKGROUND: There are long patient waiting lists for specialist care. A dermatology dialogue service between primary and secondary care (DDPS) was developed in eastern England. Primary care referrers uploaded patient images of skin conditions for review by and dialogue with consultant dermatologists in an attempt to retain patients in primary care rather than refer them to secondary care. METHODS: Evaluation of service performance against specific targets, including reduction in secondary care waiting list growth over the period April 2021-March 2022 inclusive. Service activity was summarized in terms of speed of resolution, case numbers, and dispositions. Clinician and patient satisfaction were assessed using structured questionnaires. Actual numbers of new referrals were compared to projections based on historical data. Waiting list growth was compared to other specialties and other commissioning areas. Waiting times to initial treatment were monitored. RESULTS: Over 3300 patients were enrolled and > 90% of dialogues were resolved within 36 hours. Clinician and patient satisfaction were high. Frequently asked questions and conditions were highlighted by dermatologists to design and deliver an educational event for primary care clinicians that was well received. Waiting list growth for dermatology patients in the commissioning area was smaller than for other major specialties, and generally smaller than growth for dermatology waiting lists commissioned by other NHS commissioners. There was no negative impact on the urgent priority (cancer pathway) waiting list. CONCLUSION: The DDPS was satisfactory for clinicians and patients and coincided with lower growth in dermatology waiting lists than might otherwise have been expected.

An agent-based model about the effects of fake news on a norovirus outbreak.

BACKGROUND: Concern about health misinformation is longstanding, especially on the Internet. METHODS: Using agent-based models, we considered the effects of such misinformation on a norovirus outbreak, and some methods for countering the possible impacts of "good" and "bad" health advice. The work explicitly models spread of physical disease and information (both online and offline) as two separate but interacting processes. The models have multiple stochastic elements; repeat model runs were made to identify parameter values that most consistently produced the desired target baseline scenario. Next, parameters were found that most consistently led to a scenario when outbreak severity was clearly made worse by circulating poor quality disease prevention advice. Strategies to counter "fake" health news were tested. RESULTS: Reducing bad advice to 30% of total information or making at least 30% of people fully resistant to believing in and sharing bad health advice were effective thresholds to counteract the negative impacts of bad advice during a norovirus outbreak. CONCLUSION: How feasible it is to achieve these targets within communication networks (online and offline) should be explored.

Brush cytology vs. endoscopic biopsy for the surveillance of Barrett's esophagus.

BACKGROUND AND STUDY AIMS: Periodic surveillance with systematic biopsies is recommended for patients with Barrett's esophagus. Brush cytology has been proposed as a simple inexpensive component of endoscopic surveillance, which may also detect abnormalities prior to detection of histologic abnormalities. The aim of the current study was to determine whether brush cytology provides any additional value over endoscopic surveillance biopsies in patients with Barrett's esophagus. PATIENTS: This retrospective cohort study included 530 patients with Barrett's esophagus undergoing endoscopic surveillance with paired biopsy and cytology specimens at the Cleveland Clinic between January 1994 and July 2008. The main outcome measures were sensitivity, specificity, and concordance rates of cytology and histology. RESULTS: Sensitivity of cytology for any dysplasia was 49 % and specificity was 95 %. However, sensitivity was 82 % for detection of high grade dysplasia/adenocarcinoma but only 31 % for low grade/indefinite for dysplasia. The concordance rate between cytology and histology was 80 %. Histology had a higher dysplasia detection rate than cytology (24.0 % vs. 15.7 %, respectively; P <0.0001). CONCLUSIONS: Cytology has excellent specificity and good sensitivity for the detection of high grade dysplasia/adenocarcinoma but poor sensitivity for low grade dysplasia. There was substantial concordance between cytology and histology for the detection of dysplasia. However, histology had a higher dysplasia detection rate and therefore the value of routine cytology in the surveillance of Barrett's esophagus is questionable.

Prostate cancer specific integrin alphavbeta3 modulates bone metastatic growth and tissue remodeling.

The management of pain and morbidity due to the spreading and growth of cancer within bone remains to be a paramount problem in clinical care. Cancer cells actively transform bone, however, the molecular requirements and mechanisms of this process remain unclear. This study shows that functional modulation of the alphavbeta3 integrin receptor in prostate cancer cells is required for progression within bone and determines tumor-induced bone tissue transformation. Using histology and quantitative microCT analysis, we show that alphavbeta3 integrin is required not only for tumor growth within the bone but for tumor-induced bone gain, a response resembling bone lesions in prostate cancer patients. Expression of normal, fully functional alphavbeta3 enabled tumor growth in bone (incidence: 4/4), whereas alphavbeta3 (-), inactive or constitutively active mutants of alphavbeta3 did not (incidence: 0/4, 0/6 and 1/7, respectively) within a 35-day-period. This response appeared to be bone-specific in comparison to the subcutis where tumor incidence was greater than 60% for all groups. Interestingly, bone residing prostate cancer cells expressing normal or dis-regulated alphavbeta3 (either inactive of constitutively active), but not those lacking beta3 promoted bone gain or afforded protection from bone loss in the presence or absence of histologically detectable tumor 35 days following implantation. As bone is replete with ligands for beta3 integrin, we next demonstrated that alphavbeta3 integrin activation on tumor cells is essential for the recognition of key bone-specific matrix proteins. As a result, prostate cancer cells expressing fully functional but not dis-regulated alphavbeta3 integrin are able to control their own adherence and migration to bone matrix, functions that facilitate tumor growth and control bone lesion development.

Transfer of phosphatidylcholine facilitated by a component of human plasma.

A constituent of lipoprotein-free (p greater than 1.21) human plasma from normolipemic donors facilitates the transfer of diacyl phosphatidylcholine from unilamellar egg yolk phosphatidylcholine liposomes to liver mitochondria. The active component is heat labile, has a hydrated density greater than 1.25 and an apparent molecular weight of more than 100 000. The presence of this protein in plasma may facilitate movement of diacylphospholipids between the surfaces of lipid-containing particles such as lipoproteins and erythrocytes. Knowledge of the properties and behavior of this protein are important in designing methods of drug therapy based on encapsulation in biodegradable lipid vesicles.

Stromal tumors of the jejunum and ileum: a clinicopathologic study of 39 cases.

Recently, cell size, cell density, and growth pattern were found to be reliable histologic parameters in separating benign from malignant duodenal stromal tumors. However, there are few data on the histologic features and important prognostic parameters of stromal tumors from other parts of the small bowel. Thus, we studied the clinical and pathologic features of 39 stromal tumors of the jejunum and ileum to determine which parameters would be most useful in distinguishing a benign from a malignant tumor. In all cases, the following histologic parameters were recorded: (a) predominant growth pattern (organoid, fascicular, solid, or mixed), (b) cellularity (low or high), (c) predominant cell type (spindled, epithelioid, or mixed), (d) nuclear pleomorphism (minimal, moderate, or severe), (e) the presence or absence of tumor cell necrosis, (f) the presence or absence of mucosal infiltration, (g) the presence or absence of skeinoid fibers, and (h) the number of mitotic figures per 50 high-power microscopic fields (HPF). Clinical follow-up was obtained in all cases, and the patients were considered to have suffered an adverse outcome if they developed metastatic disease or died as a complication of their tumor. In the absence of these features, patients were not considered to have suffered an adverse outcome. Twenty-five patients suffered an adverse outcome. Twenty-one patients died of disease from 1 month to 9 years (median: 2 years). One patient died at 4 days because of postoperative complications. Three patients were alive with metastatic disease at 6 months, 6 years, and 7 years. Twenty-four of these 25 patients developed metastatic disease, most commonly to the liver. Fourteen patients did not suffer an adverse outcome. Eleven patients were alive without disease from 2 to 11 years (median: 3 years), and three patients died of unrelated causes at 1, 1, and 3 years. Although there was some overlap in features between clinically benign and malignant tumors, features that were significantly associated with an adverse outcome included tumor size > 5 cm, mitotic counts > 5 mitotic figures per 50 HPF, high cellularity, the absence of a predominant organoid growth pattern, the absence of skeinoid fibers, the presence of severe nuclear pleomorphism, and the presence of mucosal infiltration and tumor cell necrosis (p < 0.05 using the chi-square and Fisher's exact tests). Features that were significantly associated with decreased survival included tumor size > 5 cm, mitotic counts > 5 mitotic figures per 50 HPF, high cellularity, the absence of skeinoid fibers, and the presence of tumor cell necrosis (p < 0.05 using the Mantel-Haenszel log-rank test). Given the fact that there is some overlap in these features between clinically benign and malignant tumors, a multiparametric analysis using the above features is the most effective way of predicting clinical behavior.

Proliferative epidermal lesions associated with anogenital Paget's disease.

A series of 35 cases of Paget's disease (PD) of the vulva and perianal area were studied to characterize the spectrum of proliferative epidermal lesions that occur in this rare disease but generally have been overlooked. The study group consisted of 8 men and 27 women with a median age of 66 years. Nineteen patients (54%) had one or more benign proliferative epidermal lesions, including 7 of 22 patients (32%) with vulvar PD and 12 of 13 patients (92%) with perianal PD. Two patients also had malignant squamous cell neoplasms. Three categories of epidermal hyperplasia were identified: (1) squamous hyperplasia NOS (34%), (2) fibroepithelioma-like hyperplasia (32%), and (3) papillomatous hyperplasia (29%). Small nests of hyperplastic squamous cells protruding into the dermis simulated microinvasive squamous carcinoma in three of these cases. None of the nine papillomatous hyperplasias tested for HPV by in-situ hybridization were positive. The squamous hyperplasia NOS and the papillomatous hyperplasia did not show a predilection for an anatomic site. In contrast, fibroepithelioma-like hyperplasia occurred in 69% of perianal PD compared with only 9% of vulvar cases. There was no association between the type of epidermal hyperplasia and the presence of a regional internal cancer. Two patients with vulvar PD had malignant squamous lesions, including one with squamous cell carcinoma in-situ (CIS) of classic type and one patient with invasive squamous cell carcinoma (InvSCC); the latter also had invasive PD. The malignant squamous component in both patients was positive for HPV 16/18, whereas the associated Paget's cells were HPV-negative. The finding of fibroepithelioma-like hyperplasia in the anogenital skin should prompt a thorough search for Paget' s cells. Papillomatous hyperplasia may be misinterpreted as condyloma acuminatum when Paget's cells are few in number and have koilocytotic-like vacuolar change or for warty (condylomatous) carcinoma when pseudoinvasive foci are present. When Paget's cells are florid and diffusely infiltrate an acanthotic epidermis, classic CIS may be misdiagnosed. Cytokeratin 7 immunostain is an excellent marker for intraepithelial and invasive Paget's cells that aids in their distinction from hyperplastic and malignant squamous cells.

Adenoid basal epitheliomas of the uterine cervix: a reevaluation of distinctive cervical basaloid lesions currently classified as adenoid basal carcinoma and adenoid basal hyperplasia.

A series of 12 adenoid basal carcinomas and three adenoid basal hyperplasias of the cervix were analyzed. The ages of the patients with adenoid basal carcinoma ranged from 30 to 91 years with a mean of 71 years. Pap smear results for 11 of 12 (92%) were abnormal. Almost all patients were asymptomatic. None had a gross cervical tumor. All tumors had typical histologic features of adenoid basal carcinoma, with various degrees of squamous differentiation. Depth of tumor invasion ranged from 2 mm to 10 mm (mean, 4.3 mm; median, 3.7 mm), exceeding 3 mm in six tumors (50%). Tumor volume was >500 mm3 in four tumors (33%). An associated neoplastic squamous lesion was present in 92% of patients, including high-grade cervical intraepithelial neoplasia in 10 cases and microinvasive squamous cell carcinoma in one. Treatment was predominantly surgical, usually after some form of cervical conization; conization alone was performed in three patients. Lymph nodes were removed in five patients; none of 104 nodes had metastases. No recurrence of tumor developed in any patient. Nine patients were alive without disease after 4 to 82 months (mean, 30 months), and three died without disease after 24, 63, and 87 months. The three patients with adenoid basal hyperplasia also were asymptomatic and did not have a gross cervical lesion. Pap smear results for two patients were abnormal. The adenoid basal hyperplasias were incidental, very superficial lesions that resembled small adenoid basal carcinomas. Generally, they were attached to the squamous or endocervical mucosal epithelium; all were less than 0.5 mm in depth. Treatment was hysterectomy in one patient and conization in two. Follow-up was short but uneventful. Our findings, together with those previously reported, indicate (1) adenoid basal carcinoma with typical histologic features is not a malignant neoplasm in that it typically presents in asymptomatic women, usually is discovered after an abnormal Pap smear result due to cervical intraepithelial neoplasia, does not produce a grossly visible lesion, has never metastasized to regional lymph nodes or elsewhere, and has never itself caused death; (2) rare, histologically atypical tumors with distinctly malignant features should not be regarded as adenoid basal carcinoma; and (3) adenoid basal hyperplasia probably is a small adenoid basal carcinoma. We propose the term "adenoid basal epithelioma" to replace adenoid basal carcinoma and adenoid basal hyperplasia, because it better describes the clinicopathologic features of these distinctive lesions and their excellent prognosis and may reduce the likelihood of unnecessarily aggressive treatment.

Gastric mucosal calcinosis. Calcified aluminum phosphate deposits secondary to aluminum-containing antacids or sucralfate therapy in organ transplant patients.

We have noticed calcium deposits (gastric mucosal calcinosis, or GMC) in the superficial gastric mucosa of 28 organ transplant patients (OTPs) (11 liver, seven bone marrow, four kidney, three kidney/pancreas, two heart, and one each of liver and kidney transplant) who underwent endoscopic biopsies. The deposits were tinctorially similar to cytomegalovirus inclusions, ranged from 40 to 250 mu in diameter, and were present just beneath the surface epithelium at the tips of the foveolae. An x-ray microanalysis showed that these mucosal deposits contained the elements aluminum, phosphorus, calcium, and chlorine. Clinical chart review showed that all OTPs with GMC were taking aluminum-containing antacids or sucralfate. Review of biopsies from gastric ulcer patients found GMC in a significantly smaller percentage than in transplant patients (32.7% vs. 5.1%, p < 0.0002). In addition, all three ulcer patients with calcified deposits were chronic renal failure patients on long-term aluminum-containing antacid therapy. Gastric mucosal calcinosis appears to be caused by aluminum phosphate accumulation secondary to antacid or sucralfate therapy in organ transplant patients. The presence of GMC in OTPs and chronic renal failure patients rather than other gastric ulcer patients is most likely due to the longer duration of therapy with aluminum-containing compounds in the former two patient groups. The clinical relevance of GMC remains to be seen. In theory, however, accelerated bone demineralization via loss of phosphates and absorption of aluminum in the gastrointestinal tract may be a consequence of long-term aluminum-containing antacid or sucralfate therapy.

Detection of cytomegalovirus in liver transplant biopsies. A comparison of light microscopy, immunohistochemistry, duplex PCR and nested PCR.

The polymerase chain reaction was used to detect cytomegalovirus (CMV) in 91 formalin-fixed paraffin-embedded needle biopsies from 38 liver transplant patients with allograft dysfunction. Thirty donor liver biopsies served as negative controls. PCR results were compared with light microscopy (LM), immunohistochemical staining (IH) for CMV early and late antigen, and clinical data. Primers to the major immediate early gene (MIE) and the viral DNA polymerase gene were duplex amplified. PCR product was reamplified with a nested primer set for the MIE and confirmed by electrophoretic mobilities and dot blotting. Primers for human beta-hemoglobin were used as internal controls. Seventeen of 38 patients had clinical evidence of cytomegalovirus disease, 12 of these were IH-positive, 14 were LM-positive, 15 were duplex PCR-positive and 17 were nested PCR-positive. In addition, duplex PCR was positive in one patient without other evidence of CMV disease, while nested PCR was positive in 12 such patients. The sensitivity and negative predictive value of nested PCR was 100%--however, the specificities and positive predictive values were only 42.9 and 58.6%, respectively. The control group was completely negative by LM, IH, and duplex PCR, however, 6 of 30 patients were nested PCR-positive. The number of nested-positive, duplex-negative patients without CMV disease was significantly greater in the transplant group versus the control group (12/21 vs. 6/30, P < 0.009). The incidence of IgG seropositivity was also significantly greater in the transplant group versus the controls (29/32 vs. 15/24, P < 0.02). We conclude that nested PCR may be an overly sensitive technique for the detection of clinically relevant CMV disease. A negative nested PCR assay for CMV may, however, help rule-out symptomatic CMV infection in an individual case. Duplex PCR showed little advantage over LM, while IH was confirmatory but did not add any new information in this study.

Evaluation of superoxide dismutase (orgotein) in medical treatment of canine cataract.

Orgotein (Palosein) is a veterinary product with marked superoxide dismutase activity that has been used intracamerally to treat senile cataracts in the dog. Fourteen old dogs with bilateral senile cataracts were injected twice in one eye with orgotein and twice in the other eye with isotonic saline under masked conditions. Observations were made over an average of a 12-week period. No clearing of lenses could be detected and there was no observed subjective improvement in the dogs' visual behavior.

Enterocele: is there a histologic defect?

OBJECTIVE: To examine the histology of the vaginal wall in women with an enterocele confirmed by physical examination, cystoproctography, and intraoperative exploration. METHODS: Thirteen women with posthysterectomy apical and posterior wall prolapse were evaluated with a detailed physical examination, cystoproctography, and intraoperative exploration. All women had enterocele repair. A specimen of full thickness vaginal wall from the leading edge of the enterocele was excised and examined histologically. The histology of these patients was compared with the histology of two comparison groups, five women undergoing hysterectomy without prolapse and 13 women undergoing radical hysterectomy. RESULTS: One woman with an enterocele repaired intraoperatively did not have an enterocele by cystoproctography. One woman with an enterocele repaired intraoperatively did not have an enterocele detected by physical examination. All women with an enterocele repaired had an intact vaginal wall muscularis. No woman had vaginal wall epithelium in direct contact with the peritoneum. The average vaginal wall muscularis thickness in women with enteroceles was 3.5 +/- 1.4 mm, in women with no prolapse 3.2 +/- 0.8 mm, and in women undergoing radical hysterectomy 2.8 +/- 0.9 mm. CONCLUSION: Women with enteroceles have a well-defined vaginal muscularis between the peritoneum and vaginal epithelium.

Ventricular fibrillation without left ventricular venting. Observations in humans.

Pressures were measured in the heart and great vessels of 52 patients who underwent coronary revascularization. In 25 patients the left ventricle was vented during fibrillation; in the others a vent was not used. Samples for blood gas analysis were obtained twice during fibrillation from the aorta, left atrium, pulmonary artery, and right atrium. Left ventricular venting was found to be effective in keeping mean left heart pressure below 10 mm Hg, although temporary incompetence of the aortic valve or malfunction of the vent occasionally caused higher pressures. Vent use led to air embolism in the aorta in 16% of the patients. In the nonvented patients mean left heart pressures remained between 10 and 20 mm Hg. However, higher values were frequently observed. Blood gas analysis demonstrated that without venting, retrograde pulmonary flow occurred during fibrillation. No abnormality was encountered that could be related to nonventing.

Limiting long-term illness and its associations with mortality and indicators of social deprivation.

STUDY OBJECTIVE: To examine geographical variation in limiting long-term illness in England and Wales and assesses the extent of its similarity with the distribution of mortality rates and of deprivation. DESIGN: A geographically based study using data from the 1991 census on limiting long term illness. Maps and regression analysis are used to compare the distribution of standardised illness ratios with standardised mortality ratios and indicators of social deprivation. SETTING: A total of 401 local authority districts in England and Wales. PARTICIPANTS: The population of England and Wales enumerated in the 1991 census. MAIN RESULTS: The geographical pattern of limiting long term illness shows many similarities with that of mortality but there are also some differences. Both are positively associated with indicators of social deprivation, with limiting long term illness tending to show stronger correlations, particularly in the elderly. Most of Wales and many industrial areas of northern England have higher rates of long term illness than would be expected from their mortality rates, while much of south eastern England has lower than expected rates. CONCLUSIONS: Moves towards using data on limiting long term illness instead of standardised mortality rates would have important implications for NHS resource allocations. Further assessment of the reliability of these data on self reported morbidity is required. in particular, there is a need to assess how much they reflect real differences in ill health rather than the influence of socioeconomic or cultural factors affecting the likelihood of a positive answer to the census question on limiting long term illness.

Changing health beliefs and behaviors of resettled Laotian refugees: ethnic variation in adaptation.

This paper describes traditional and changing health-related beliefs and behaviors of ethnic Lao refugees now resettled in the United States and how these compare with those of other ethnic groups of resettled refugees from Southeast Asia. New data are presented for Southeast Asian refugees resettled in Franklin County, Ohio, including resettlement agency utilization statistics for refugees of each local ethnic group, which reveal that Laotian refugees have the most persistent use of resettlement agency services. The results of in-depth, open ended interviews with members of the Franklin County Lao community are also presented. The interview data pertain to Lao self-perceived health problems and health care options as well as their health beliefs and practices, both traditionally in Laos and as these have changed with refugee flight and resettlement. These data are compared with the results of the limited relevant health-related research on other ethnic groups of Southeast Asian refugees, revealing that Laotian refugees rely to a relatively great extent on the Western biomedical system. It is suggested that the nature of Lao refugee adaptation is due to the continuation of traditional patron-client relationships in the U.S., with Lao patrons referring their refugee clients to the services of agencies and the biomedical establishment.

Frozen section evaluation of stereotactic brain biopsies: diagnostic yield at the stereotactic target position in 188 cases.

OBJECTIVE: Use of the image-guided stereotactic brain biopsy has facilitated the diagnosis of previously inaccessible lesions with both safety and reliability. However, few studies have assessed the diagnostic yield of frozen section evaluation of the initial stereotactic target (FS-0). We describe our experience with 188 stereotactic brain biopsies in order to evaluate the diagnostic yield of FS-0. DESIGN: Retrospective study of 188 stereotactic brain biopsies from 185 patients. SETTING: Tertiary referral center with a high volume of neurosurgical cases including image-guided stereotactic brain biopsies. PATIENTS: One hundred eighty-five patients who underwent imaged-guided stereotactic brain biopsy over a 58-month period. RESULTS: The patients studied included 107 males and 78 females (mean age 48 years). Eleven (6%) biopsies were nondiagnostic. Diagnoses from FS-0 included a neoplastic condition in 96 (73%) of 131 cases and a nonneoplastic condition in 23 (50%) of 46 cases. In 119 (67%) of 177 cases, a diagnosis was reached at FS-0. A correct diagnosis was made on subsequent frozen section in 28 (16%) of cases, including 21 (16%) of 131 neoplasms and 7 (15%) of nonneoplastic conditions. In 15 (54%) of 28 cases, the correct diagnosis was made on the second frozen section; in 25 (89%) of 28, the correct diagnosis was made by the fourth frozen section. In 14 (11%) of 131 neoplastic cases, a sampling error relative to the lesion resulted in an inaccurate diagnosis at FS-0. A significant error in diagnosis occurred in three cases (1.7%). CONCLUSIONS: We conclude that (1) because 58 (33%) of 177 diagnosed cases in our series would have been potentially misdiagnosed if only one biopsy had been taken at the stereotactic target, frozen section evaluation or cytologic examination of material at the time of surgery should be performed routinely to ensure that adequate tissue has been obtained for purposes of diagnosis; (2) taking up to four biopsies increases the diagnostic yield (from 67% to 89% in this series); and (3) neoplastic lesions are more likely to be definitively diagnosed at FS-0 than non-neoplastic lesions.

Comparison of ward population estimates from FHSA patient registers with the 1991 Census.

"Postcode addresses from National Health Service patient registers for Norfolk and Suffolk [counties in England] current on census day 1991 were assigned to census wards, and estimates of populations in wards were produced for the total population and for twelve age-sex groups. These were compared with adjusted counts of usual residents from the 1991 Census." The results indicate that family health service authority registers "are an acceptable alternative to the census for population estimation purposes. This supports recent arguments for wider use of population registers and suggests that they may be particularly valuable as a source of intercensal information."