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Biomedical subjects

J M Horsman

Publications and source records attributed to J M Horsman.

14 recordsLinked to original sources

Current management of treatment-induced bone loss in women with breast cancer treated in the United Kingdom.

New therapeutic options in breast cancer have improved survival but consequently increase the relevance of late complications. Ovarian suppression/ablation and aromatase inhibitors (AI) in the adjuvant setting have improved outcome, but have clinically important adverse effects on bone health. However, investigation and management of cancer treatment-induced bone loss (CTIBL) is poorly defined with no national guidance. In 2004, a questionnaire was sent to over 500 breast surgeons and oncologists who treat breast cancer within the United Kingdom. The questionnaire evaluated access to bone densitometry and specialist expertise as well as attitudes to investigation of CTIBL and anticipated changes in the use of AI for postmenopausal early breast cancer. A total of 354 completed questionnaires were received, 47 from clinicians not currently treating breast cancer. Of the 307 evaluable questionnaires, 164 (53%) were from breast surgeons, 112 (36%) from clinical oncologists and 31 (10%) from medical oncologists. Although most respondents recognised that CTIBL was the responsibility of the treating breast team, investigations for CTIBL are limited even though most had adequate access to bone densitometry; 98 (32%) had not requested a DXA scan in the last 6 months and 224 (73%) had requested fewer than five scans. In all, 235 (76%) were not routinely investigating patients on AI for bone loss. A total of 277 (90%) felt that their practice would benefit from national guidelines to manage these patients, and the majority (59%) had little or no confidence in interpreting DXA results and advising on treatment. This questionnaire has highlighted clear deficiencies in management of CTIBL in early breast cancer. The development of national guidelines for the management of these patients and educational initiatives for breast teams are urgently required.

Aged↗

Primary bone lymphoma: a retrospective analysis.

The aim of this study was to retrospectively define those patients with unequivocal primary bone lymphoma presenting to the Sheffield Lymphoma Group and document patient and tumour characteristics and management strategies, and correlate these with survival. Thirty-seven patients were documented from a total of 3148 cases of non-Hodgkin's lymphoma seen over 34 years. There were 17 males and 20 females, with a mean age of 55.4 years (range, 27-78). Pain was the most commonly presented symptom (67.5%), and the pelvis was the most frequently presented site (21.3%). Grade 2 and diffuse large B cell lymphoma comprised the majority of histologies (78.7% and 70.3%, respectively). Treatment was most often with radiotherapy alone (41.8%) or combined with CHOP-like chemotherapy (37.9%). The overall response rate was 56.7%, and 5- and 10-year survival rates were 64.5% and 49.6%, respectively. Univariate analysis showed an age of <60 years and complete response to be favourable prognostic factors. There was a trend toward better survival with combined modality therapy involving CHOP-like chemotherapy. Bone lymphoma has a better survival than other extranodal lymphomas. Younger age and complete response are favourable predictive factors. Combined modality treatment is likely to be the treatment of choice but this remains to be confirmed in large prospective multicentre studies.

Adult↗

Second primary malignancies after treatment for malignant lymphoma.

To determine the incidence and possible causes of second primary malignancies after treatment for Hodgkin's and Non-Hodgkin's lymphoma (HL and NHL). A cohort of 3764 consecutive patients diagnosed with HL or NHL between January 1970 and July 2001 was identified using the Sheffield Lymphoma Group database. A search was undertaken for all patients diagnosed with a subsequent primary malignancy. Two matched controls were identified for each case. Odds ratios were calculated to detect and quantify any risk factors in the cases compared to their matched controls. Mean follow-up for the cohort was 5.2 years. A total of 68 patients who developed second cancers at least 6 months after their primary diagnosis were identified, giving a crude incidence of 1.89% overall: 3.21% among the patients treated for HL, 1.32% in those treated for NHL. Most common were bronchial, breast, colorectal and haematological malignancies. High stage at diagnosis almost reached statistical significance in the analysis of just the NHL patients (odds ratio = 3.48; P = 0.068) after adjustment for other factors. Treatment modality was not statistically significant in any analysis. High stage at diagnosis of NHL may be a risk factor for developing a second primary cancer.

Case-Control Studies↗

Localised extranodal lymphoma of the head and neck: the Sheffield Lymphoma Group experience (1971-2000).

AIMS: Over the 30-year period from 1971-2000, 3750 cases of lymphoma were referred to the Sheffield Lymphoma Group for investigation and treatment. Of these, 580 were extranodal presentations and, of these, 190 (33%) were localised to the head and neck region. The aim of this lymphoma database review was to evaluate the patient characteristics and survival rates for these patients. MATERIALS AND METHODS: The sample included 98 women and 92 men, with a median age at presentation of 65 years. RESULTS: The most common site affected was tonsil (34%), followed by salivary glands (16%). Other common sites were the thyroid, orbit and nasopharynx. The most frequent presenting feature was a swelling or mass, with pain, dysphagia and nasal obstruction also comprising large groups. All cases were non-Hodgkin's lymphoma. Fifty-five cases were histological grade 1; 132 were grade 2. Diffuse large B cell was the most common histological subtype. The overall 5- and 10-year survival rates were 55% (95% CI 47-62) and 44%, (95% CI 36-53), respectively, with a median survival of 92 months (95% CI 56-128). Stage and grade were both found to influence survival. CONCLUSION: This data concords with and extends information available from previous studies. More detail is now required on specific head and neck sites.

Adolescent↗

The management and survival of patients with advanced germ-cell tumours: improving outcome in intermediate and poor prognosis patients.

AIMS: The survival of germ-cell tumours (GCT) was transformed after the introduction of cisplatin-based therapy. Previous trials have indicated BEP (bleomycin, etoposide and cisplatin) as the optimum treatment, although some centres including our own advocate the use of the alternating regimen POMB-ACE (cisplatin, vincristine, methotrexate, bleomycin and dactinomycin, cyclophosphamide and etoposide) for men with intermediate or poor prognosis disease. We analysed the survival and management of GCT patients treated at a specialist cancer centre in relation to internationally recognised prognostic groupings. MATERIALS AND METHODS: We retrieved patient information using the Trent Testicular Tumour Registry and supplemented it with information from patient notes. This included all patients with Royal Marsden Hospital Stage II, III and IV disease and patients with stage I disease at diagnosis with raised markers or subsequent relapse. We compared the efficacy and toxicity of the BEP and POMB-ACE chemotherapy regimens, and assessed relapse-free and overall survival. RESULTS: We identified 178 non-seminomatous germ cell tumours (NSGCT) and 71 seminoma patients. Overall survival was similar to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification for the good (95% vs 92%) and intermediate groups (82% vs 80%). The outcome for the poor prognosis group was better than expected in our series (57% vs 48%). There was a higher proportion of both immediate and late side-effects with POMB-ACE. CONCLUSION: Survival and disease progression rates at this single institution were at least as good as reported by the IGCCCG and somewhat better for the poor-prognosis group. This may reflect use of the POMB-ACE chemotherapy regimen as opposed to standard BEP regimen. However, a randomised comparison of BEP and POMB-ACE would be required to validate this.

Adolescent↗

Is there a relationship between treatment for infertility and gestational trophoblastic disease?

BACKGROUND: The aim of the study was to record the incidence of treatment for infertility prior to development of gestational trophoblastic disease (GTD). METHODS AND RESULTS: A retrospective analysis was undertaken of 231 consecutive women receiving chemotherapy for persistent GTD at Weston Park Hospital, Sheffield, from 1991 to 2001. Three patients in this group had received treatment for infertility prior to their molar pregnancy. In a control group of 226 patients not requiring treatment for persistent GTD, four had had treatment for infertility just before their molar pregnancy, and in a further control group of 208 'normal' pregnancies, eight patients had had treatment for infertility prior to conception. CONCLUSION: We conclude that we can demonstrate no relationship between infertility treatment and subsequent development of GTD.

Adult↗

Adjuvant interferon in high-risk melanoma: the AIM HIGH Study--United Kingdom Coordinating Committee on Cancer Research randomized study of adjuvant low-dose extended-duration interferon Alfa-2a in high-risk resected malignant melanoma.

PURPOSE: To evaluate low-dose extended duration interferon alfa-2a as adjuvant therapy in patients with thick (> or = 4 mm) primary cutaneous melanoma and/or locoregional metastases. PATIENTS AND METHODS: In this randomized controlled trial involving 674 patients, the effect of interferon alfa-2a (3 megaunits three times per week for 2 years or until recurrence) on overall survival (OS) and recurrence-free survival (RFS) was compared with that of no further treatment in radically resected stage IIB and stage III cutaneous malignant melanoma. RESULTS: The OS and RFS rates at 5 years were 44% (SE, 2.6) and 32% (SE, 2.1), respectively. There was no significant difference in OS or RFS between the interferon-treated and control arms (odds ratio [OR], 0.94; 95% CI, 0.75 to 1.18; P =.6; and OR, 0.91; 95% CI, 0.75 to 1.10; P =.3; respectively). Male sex (P =.003) and regional lymph node involvement (P =.0009), but not age (P =.7), were statistically significant adverse features for OS. Subgroup analysis by disease stage, age, and sex did not show any clear differences between interferon-treated and control groups in either OS or RFS. Interferon-related toxicities were modest: grade 3 (and in only one case, grade 4) fatigue or mood disturbance was seen in 7% and 4% respectively, of patients. However, there were 50 withdrawals (15%) from interferon treatment due to toxicity. CONCLUSION: The results from this study, taken in isolation, do not indicate that extended-duration low-dose interferon is significantly better than observation alone in the initial treatment of completely resected high-risk malignant melanoma.

Adolescent↗

Peripheral T cell lymphoma: The Sheffield Lymphoma Group experience (1977-2001).

Peripheral T-cell lymphomas (PTCL) account for approximately 10% of all non-Hodgkin's lymphomas. The aim of this retrospective study was to analyse the presentation, management, outcome and significant prognostic factors in a large series of patients with PTCL. It includes 104 consecutive patients who presented to the Sheffield Lymphoma Group between 1977 and 2001. Clinical parameters were recorded for each subgroup. End points were response to treatment and survival. Survival analysis was used to assess the prognostic value of the variables. PTCL not otherwise specified contributed 52% of cases followed by anaplastic large cell lymphoma with 17% and angiocentric type with 13% of cases. The overall complete remission (CR) of the series was 59%. Stage at diagnosis affected response to treatment with 81% of cases in stage 1 and 2 achieving CR compared to 43% in stages 3 and 4 (p</=0.001). Extranodal presentations also showed a favourable response with 74% obtaining CR compared to 46% of nodal presentations (p<0.01). Median survival of all patients was 87 months with a five-year probability of survival of 52%. Variables found to be related to poor outcome are age >60 years (p<0.05), high grade histology (p<0.001), presence of B symptoms (p<0.005), nodal presentation (p<0.005) and advanced stage at diagnosis (p<0.001). Histological sub-type did not significantly correlate to outcome. In conclusion whilst a number of prognostic indicators can assist in determining the outcome in PTCL, these lymphomas are complex and often follow an unpredictable course. In order to make the best clinical decisions in individual cases, more clinical study is required.

Female↗

Localised extranodal non-Hodgkin's lymphoma of the gastrointestinal tract: Sheffield Lymphoma Group experience (1989-1998).

Extranodal non-Hodgkin's lymphoma (NHL) of the gastrointestinal tract accounts for about one third of all extranodal NHL. We retrospectively reviewed the clinical and histopathologic records of 71 patients with stage IE and IIE primary gastrointestinal NHL referred to the Sheffield Lymphoma Group (SLG) from 1989 to 1998. Cross-referencing with the Hospital Histopathology Department database revealed that only two-thirds of all cases were seen by the Group. The most common primary site was the stomach (45 patients, 63% of all cases), followed by the small intestine (16, 23%) and large intestine (9, 13%). The median age of patients was 62 years; the majority of patients presented with stage I (61%) and/or grade (65%) NHL. Mucosa-associated lymphoid tissue (MALT) lymphomas were the largest histologic subtype seen (57%), with 87% of these arising from the stomach; next most frequent was the diffuse large B-cell subtype (21% of all cases) most frequently arising from the intestine (60%). For treatment of gastric MALT lymphoma, a combined approach (surgery followed by chemotherapy, antihelicobacter therapy followed by chemotherapy) was favoured (22 cases). Five-year and 10-year overall survivals were 52% and 45% respectively. Knowledge of the Revised European American Lymphoma classification and the Helicobacter pylori/MALT association has influenced treatment approaches over the 10-year study period. For small intestinal lymphoma, surgery (with or without chemotherapy) gave 5- and 10-year survivals of 60%. Overall survival of patients with primary gastrointestinal lymphoma managed by the SLG is similar to that reported from other large series.

Adult↗

Non-Hodgkin's lymphoma presenting with spinal involvement: the Sheffield Lymphoma Group experience (1970-2000).

Spinal non-Hodgkin's lymphoma is rare. We retrospectively reviewed the clinical and histopathologic records of 39 consecutive patients referred to the Sheffield Lymphoma Group from 1970 to 2000 and analysed the prognostic differences between localised (stage IE and IIE) and secondary (stage III and IV) spinal non-Hodgkin's lymphoma (S-NHL) patients. Forty-five percent of all patients were over 60 years old. More patients were male (58%); presented with stage IE and IIE (63%), mostly of intermediate/high grade histology (74%); over a third had symptoms; nearly a third (11 patients) were paraplegic and 14 had sphincter dysfunction at diagnosis. The overall survival of all patients was 39% at 5 years (median 24.7 months), whilst that of localised S-NHL was 51% (median 89.7 months). Univariate analysis showed better survival for patients with good mobility status at presentation (p < 0.0l) and complete response to initial treatment (p < 0.00l). In primary S-NHL, histology (p < 0.05) significantly influenced overall survival. In conclusion, disease is frequently locally advanced at presentation with aggressive histologic grade: thorough staging should always be performed to exclude widespread disease. Good mobility status predicts for good survival outcome. Optimal treatment is still uncertain.

Actuarial Analysis↗

Prognostic markers in malignant lymphoma: an analysis of 1,198 patients treated at a single centre.

The prognostic significance of 20 putative markers has been assessed in a consecutive series of 1,198 patients with malignant lymphoma seen by the Sheffield Lymphoma Group over three decades. Univariate analysis disclosed that ten factors for both Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) Grade I, and twelve factors for NHL Grade II had prognostic significance. However, multivariate analysis selected only three (age, serum albumin and lymphocyte count) for HD, one (serum albumin) for NHL Grade I and five (age, stage, erythrocyte sedimentation rate, serum albumin and serum lactate dehydrogenase) for NHL Grade II as independent predictors for survival. Risk adjusted prognostic models were derived for Hodgkin's disease and NHL Grade II. For Hodgkin's disease the presence of 3 risk factors predicted for only 35% long-term survival for this group of patients. For NHL Grade II the group with 3-5 risk factors present had a median survival of less than 2 years compared to a 9-year median survival in patients with 1 risk factor present. Whilst these models are being validated on a larger series of patients and will also be tested prospectively, new markers are needed to facilitate decisions on treatment for individual patients.

Adult↗

An orientation anisotropy in the effects of scaling vertical disparities.

Gårding et al. (Vis Res 1995;35:703-722) proposed a two-stage theory of stereopsis. The first uses horizontal disparities for relief computations after they have been subjected to a process called disparity correction that utilises vertical disparities. The second stage, termed disparity normalisation, is concerned with computing metric representations from the output of stage one. It uses vertical disparities to a much lesser extent, if at all, for small field stimuli. We report two psychophysical experiments that tested whether human vision implements this two-stage theory. They tested the prediction that scaling vertical disparities to simulate different viewing distances to the fixation point should affect the perceived amplitudes of vertically but not horizontally oriented ridges. The first used elliptical half-cylinders and the 'apparently circular cylinder' judgement task of Johnston (Vis Res 1991;31:1351-1360). The second experiment used parabolic ridges and the amplitude judgement task of Buckley and Frisby (Vis Res 1993;33:919-934). Both studies broadly confirmed the anisotropy prediction by finding that large scalings of vertical disparities simulating near distances had a strong effect on the perceived amplitudes of the vertically oriented stimuli but little effect on the horizontal ones. When distances > 25 cm were simulated there were no significant differential effects and various methodological reasons are offered for this departure from expectations.

Adult↗

Health care workers and HIV/AIDS: a critical review of the literature.

This paper reviews the extensive literature which looks at the impact of HIV/AIDS on health care workers (HCWs). The knowledge and attitudes of HCWs toward people with HIV/AIDS and other relevant attitudes, for example those regarding male homosexuality have been widely studied whereas attitudes to intravenous drug use are perhaps under-investigated. Three major themes of the literature are examined. These are fear of infection, beliefs about the right to refuse care and the stresses associated with caring for HIV positive people. A number of educational interventions which attempt to change HCWs attitudes and beliefs are reviewed. Some notable gaps in the literature are identified. Neglected areas include attitudes to women, people of colour and consideration of the organizational and societal factors mediating the impact of HIV upon healthcare workers. Limitations of the research techniques used are identified and future implications for health care workers are considered.

Acquired Immunodeficiency Syndrome↗

Integration of stereo, texture, and outline cues during pinhole viewing of real ridge-shaped objects and stereograms of ridges.

Three experiments are reported in which the possible role of blur cues as a factor needing to be taken into account in cue-integration studies involving conflicts between stereo and texture/outline cues was investigated. The earlier suggestion was tested that uncontrolled blur cues might have caused the quite different patterns of cue integration reported for real ridge-shaped objects oriented vertically and for stereograms depicting similar surfaces. Blur cues were manipulated by pinhole viewing intended to render accommodation open loop. The results for real ridges were as predicted by the blur-cue hypothesis: pinhole viewing strengthened texture/outline cues in vertically oriented ridges, thereby diminishing the pattern of stereo dominance hitherto observed for these stimuli (and as observed here in non-pinhole-viewing control conditions and in horizontally oriented ridges). The results for the stereograms did not conform to predictions: pinhole viewing, assumed to remove blur cues from the cue-integration process, still produced the pattern observed in control conditions in which a texture/outline cue for a shallow ridge overwhelmed stereo cues for a steep ridge. This result is against the hypothesis that perhaps blur cues for the stereogram projection surface differentially favoured the shallow texture/outline cues. A new variant of the blur-cue hypothesis is offered to account for this result. The main conclusion from the study is: beware drawing firm conclusions from stereograms about the pattern of cue integration that can be expected when real objects are being viewed. The two situations can produce very different results as far as cue integration is concerned. This is a conclusion with serious implications for the use of stereograms for studying the integration of stereo with other cues.

Adolescent↗