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1.
Br J Haematol ; 194(2): 365-377, 2021 07.
Article in English | MEDLINE | ID: mdl-33959947

ABSTRACT

Mantle cell lymphoma (MCL) presenting in elderly, unfit patients represents a clinical challenge. Front-line 'attenuated' or low-intensity immunochemotherapy is often employed, although outcomes are relatively unexplored. We report outcomes of attenuated immunochemotherapy in 95 patients with MCL across 19 centres in the UK and Ireland considered unfit for full-dose rituximab-bendamustine or rituximab-cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP). Regimens examined were rituximab-cyclophosphamide, vincristine, prednisolone (R-CVP) (n = 19), dose-attenuated R-CHOP (n = 22), dose attenuated rituximab-bendamustine (n = 24) and rituximab-chlorambucil (n = 30). The primary outcome was progression-free survival (PFS). The secondary outcomes included overall response, overall survival (OS) and toxicity. The median (range) age was 79 (58-89) years and 50% were aged ≥80 years. The median (range) Cumulative Illness Rating Scale-Geriatric score was 6 (0-24). The median PFS for all patients was 15 months [95% confidence interval (CI) 8·7-21·2) and median OS was 31·4 months (95% CI 19·7-43·2). By multivariable analysis (MVA), the only clinical factor associated with an inferior PFS was blastoid morphology [hazard ratio (HR) 2·90, P = 0·01). Notably, higher treatment intensity (R-CHOP/R-bendamustine composite) provided an independently superior PFS compared with R-CVP/R-chlorambucil (MVA HR 0·49, P = 0·02). Factors associated with inferior OS by MVA were Eastern Cooperative Oncology Group Performance Status (HR 2·14, P = 0·04), blastoid morphology (HR 4·08, P = 0·001) and progression of disease at <24 months status (HR 5·68, P < 0·001). Overall, survival after front-line dose-attenuated immunochemotherapy is unsatisfactory. Clinical trials investigating novel agents such as Bruton tyrosine kinase and B-cell lymphoma 2 inhibitors in this specific clinical setting are warranted.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/therapeutic use , Lymphoma, Mantle-Cell/drug therapy , Prednisone/therapeutic use , Rituximab/therapeutic use , Vincristine/therapeutic use , Age Factors , Aged , Aged, 80 and over , Doxorubicin/therapeutic use , Female , Humans , Immunotherapy , Ireland/epidemiology , Lymphoma, Mantle-Cell/epidemiology , Male , Middle Aged , Retrospective Studies , Survival Analysis , Treatment Outcome , United Kingdom/epidemiology
2.
BMJ Case Rep ; 20142014 Dec 24.
Article in English | MEDLINE | ID: mdl-25540208

ABSTRACT

A 48-year old woman with metastatic breast cancer and extensive bone marrow infiltration was admitted with extreme lethargy, jaundice and deranged liver function tests. She had been started on anastrozole in May 2013 for bony metastases, detected on a bone scan. A CT scan performed at that time had shown no evidence of metastatic or nodal disease elsewhere. Over the subsequent 2 months, the patient had become progressively jaundiced. Outpatient abdominal ultrasound and CT liver had shown a fatty liver with no focal lesions. She was admitted in August 2013 with bilirubin 567, alkaline phosphatase 385, alanine aminotransferase 98, albumin 25 and international normalised ratio 1.9. The patient ultimately had a liver biopsy, which demonstrated features of drug-induced steatohepatitis, and anastrozole was found to have been the probable cause. This case explores the differentials of jaundice in a patient with cancer and describes a rare cause of drug-induced liver injury.


Subject(s)
Antineoplastic Agents, Hormonal/adverse effects , Breast Neoplasms/drug therapy , Chemical and Drug Induced Liver Injury/complications , Fatty Liver/chemically induced , Jaundice/chemically induced , Liver/pathology , Nitriles/adverse effects , Triazoles/adverse effects , Anastrozole , Antineoplastic Agents, Hormonal/therapeutic use , Biopsy , Diagnosis, Differential , Female , Humans , Liver/enzymology , Liver Function Tests , Middle Aged , Nitriles/therapeutic use , Triazoles/therapeutic use
3.
BMJ Case Rep ; 20142014 Aug 21.
Article in English | MEDLINE | ID: mdl-25188923

ABSTRACT

A 71-year-old woman presented with a 2-week history of epigastric pain, nausea and vomiting; on examination she demonstrated signs of peritonism. CT imaging was performed and this demonstrated extensive thrombosis of the superior mesenteric, omental and portal veins with infarction of the distal small bowel. A non-operative approach was initiated and anticoagulation rapidly started. Within 48 h the patient demonstrated significant clinical improvement and she subsequently made a full recovery.


Subject(s)
Anticoagulants/therapeutic use , Heparin/therapeutic use , Mesenteric Veins/diagnostic imaging , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/drug therapy , Aged , Diagnosis, Differential , Female , Humans , Infarction/drug therapy , Intestine, Small/blood supply , Omentum/blood supply , Omentum/diagnostic imaging , Portal Vein/diagnostic imaging , Tomography, X-Ray Computed , Treatment Outcome , Veins
4.
J Infect Dis ; 209(1): 120-9, 2014 Jan 01.
Article in English | MEDLINE | ID: mdl-23943850

ABSTRACT

BACKGROUND: Cytoadherence and sequestration of erythrocytes containing mature stages of Plasmodium falciparum are central to the pathogenesis of severe malaria. The oral anthelminthic drug levamisole inhibits cytoadherence in vitro and reduces sequestration of late-stage parasites in uncomplicated falciparum malaria treated with quinine. METHODS: Fifty-six adult patients with severe malaria and high parasitemia admitted to a referral hospital in Bangladesh were randomized to receive a single dose of levamisole hydrochloride (150 mg) or no adjuvant to antimalarial treatment with intravenous artesunate. RESULTS: Circulating late-stage parasites measured as the median area under the parasite clearance curves were 2150 (interquartile range [IQR], 0-28 025) parasites/µL × hour in patients treated with levamisole and 5489 (IQR, 192-25 848) parasites/µL × hour in controls (P = .25). The "sequestration ratios" at 6 and 12 hours for all parasite stages and changes in microvascular blood flow did not differ between treatment groups (all P > .40). The median time to normalization of plasma lactate (<2 mmol/L) was 24 (IQR, 12-30) hours with levamisole vs 28 (IQR, 12-36) hours without levamisole (P = .15). CONCLUSIONS: There was no benefit of a single-dose of levamisole hydrochloride as adjuvant to intravenous artesunate in the treatment of adults with severe falciparum malaria. Rapid parasite killing by intravenous artesunate might obscure the effects of levamisole.


Subject(s)
Antimalarials/therapeutic use , Levamisole/therapeutic use , Malaria, Falciparum/drug therapy , Parasitemia/drug therapy , Adult , Antimalarials/pharmacokinetics , Antimalarials/pharmacology , Female , Humans , Kaplan-Meier Estimate , Lactic Acid/blood , Levamisole/pharmacokinetics , Levamisole/pharmacology , Malaria, Falciparum/metabolism , Malaria, Falciparum/parasitology , Male , Microvessels/drug effects , Middle Aged , Parasitemia/parasitology , Plasmodium falciparum/chemistry , Plasmodium falciparum/isolation & purification , Regional Blood Flow
5.
J Sex Res ; 41(2): 121-8, 2004 May.
Article in English | MEDLINE | ID: mdl-15326537

ABSTRACT

Students at a southwestern university were surveyed to test the interrelations of three constructs: sexual-moral attitudes, love styles, and attraction criteria. Following the procedures of the National Health and Social Life Survey, from which the sexual-moral attitude items were obtained, we conducted a cluster analysis to create attitudinal groupings. We obtained four clusters representing various nuances of liberalism and conservatism. When compared on love styles, the clusters differed primarily on ludus and pragma. Not only did some of the liberal clusters differ from some of the conservative ones on love styles, but there were also some differences within liberalism and within conservatism. Cluster differences also emerged on the attraction criteria.


Subject(s)
Interpersonal Relations , Marriage , Morals , Sexual Behavior/psychology , Sexual Partners/psychology , Adult , Analysis of Variance , Cluster Analysis , Female , Humans , Male , Self Concept , Sex Factors , Southwestern United States , Surveys and Questionnaires , Time Factors
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