Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I.

BACKGROUND: Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate comprising a folate receptor alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. The randomized, open-label, phase III study FORWARD I compared MIRV and investigator's choice chemotherapy in patients with platinum-resistant epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Eligible patients with 1-3 prior lines of therapy and whose tumors were positive for FRα expression were randomly assigned, in a 2 : 1 ratio, to receive MIRV (6 mg/kg, adjusted ideal body weight) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary endpoint was progression-free survival [PFS, Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, blinded independent central review] in the intention-to-treat (ITT) population and in the prespecified FRα high population. RESULTS: A total of 366 patients were randomized; 243 received MIRV and 109 received chemotherapy. The primary endpoint, PFS, did not reach statistical significance in either the ITT [hazard ratio (HR), 0.98, P = 0.897] or the FRα high population (HR, 0.69, P = 0.049). Superior outcomes for MIRV over chemotherapy were observed in all secondary endpoints in the FRα high population including improved objective response rate (24% versus 10%), CA-125 responses (53% versus 25%), and patient-reported outcomes (27% versus 13%). Fewer treatment-related grade 3 or higher adverse events (25.1% versus 44.0%), and fewer events leading to dose reduction (19.8% versus 30.3%) and treatment discontinuation (4.5% versus 8.3%) were seen with MIRV compared with chemotherapy. CONCLUSIONS: In patients with platinum-resistant EOC, MIRV did not result in a significant improvement in PFS compared with chemotherapy. Secondary endpoints consistently favored MIRV, particularly in patients with high FRα expression. MIRV showed a differentiated and more manageable safety profile than chemotherapy.

Glycaemic control and cost analysis when changing from gliclazide co-administered with metformin to pre-combined glibenclamide-metformin tablets in type 2 diabetes mellitus.

Type-2 diabetes mellitus (T2DM) patients who were on gliclazide co-administered with metformin were changed to pre-combined glibenclamide-metformin tablets in the Endocrine Clinic, Penang Hospital. We conducted a retrospective study to evaluate the differences in glycaemic control and treatment cost following the change. Eighty patients (60% females) with a mean age of 55 years old were studied. Mean glycosylated haemoglobin (HbAlc) reduction was -0.92% (p<0.01) and -0.83% (p<0.01) after three and six months respectively. Patients with baseline HbA1c > or =8% had greater reduction in mean HbA1c (-1.36%) after six months. The treatment cost per month was reduced by 45% at 3 months (p<0.01)) and 44% at 6 months (p<0.01). The change to pre-combined glibenclamide-metformin tablets resulted in significant improvement in glycaemia and reduction in treatment cost

Towards a clinical and empirical definition of burn scarring: A template analysis using qualitative data.

OBJECTIVE: This study aimed to describe the nature, scope or meaning of the concept 'burn scar', from the perspective of adults and children with burn scarring, caregivers of children with burn scarring and health professionals who were considered experts in the treatment of burn scarring. The impact of the identified characteristics on burn scar health-related quality of life (HRQOL) was also examined. METHOD: Using a phenomenological qualitative approach, 43 transcripts from semi-structured interviews with people with burn scars (n=10 adults and n=11 children), their caregivers (n=9) and health professionals (n=13) were analyzed using template analysis. RESULTS: Ten characteristics of burn scars were identified by health professionals: 'stretchability', 'hardness', 'raised', 'thickness', 'surface area', 'scar sensitivity', 'scar surface appearance', 'hydration', 'fragility', and 'color'. However, 'thickness', 'scar surface area' and 'hydration' were not described by children with burn scars and 'scar surface area' was not described by adults with burn scars or caregivers. All groups (adults, children, caregivers and health professional) perceived that the burn scar characteristics of 'stretchability' and 'scar sensitivity' impacted upon all indicators of burn scar HRQOL. The burn scar characteristics of 'fragility', 'scar surface appearance' and 'color' were largely perceived by all groups to impact upon the emotional and physical indicators of burn scar HRQOL alone. CONCLUSIONS: This study identified there are differences in the burn scar characteristics considered important by health professionals and those characteristics that adult/child/caregivers perceived to impact on indicators of burn scar HRQOL. It is recommended that outcome measures of burn scarring include the burn scar characteristics of 'stretchability' and 'scar sensitivity' at a minimum. The inclusion of 'fragility', 'scar surface appearance' and 'color' should also be considered.

Absence of mutations in DNA mismatch repair genes in sporadic endometrial tumors with microsatellite instability.

DNA mismatch repair genes have been reported to play a role in the pathogenesis of hereditary nonpolyposis colorectal cancer (HNPCC). Mutations of DNA mismatch repair genes have accounted for 90% of HNPCC-related colon and endometrial tumors. These mutations have been associated with microsatellite instability (MIN). Because endometrial cancer (EC) is the most common extracolonic malignancy associated with HNPCC, we hypothesized that similar molecular alterations may occur in sporadic endometrial tumors exhibiting MIN. Mutational analysis of the MSH2 and MLH1 genes was undertaken in sporadic EC that demonstrate MIN to determine the role of these genes in the pathogenesis of sporadic ECs. Established microsatellite markers were used to determine the incidence of MIN from 28 patients with sporadic EC. MIN was observed in 32% (9 of 28) of the tumor specimens analyzed. Mutational analysis of MSH2 and MLH1 genes was performed by immunohistochemical analysis and direct sequencing of tumor specimens that exhibited MIN. All 28 tumor specimens exhibited strong nuclear staining with both MSH2 and MLH1 antibodies, suggesting the absence of mutations. Sequencing of all exons of both the MSH2 and MLH1 genes in the nine MIN-positive tumor specimens demonstrated no mutations. We conclude that the MSH2 and MLH1 genes do not play a role in the pathogenesis of sporadic endometrial cancer.

Constant estrogen, intermittent progestogen vs. continuous combined hormone replacement therapy: tolerability and effect on vasomotor symptoms.

OBJECTIVE: To compare the efficacy and tolerability of a novel oral constant estrogen plus intermittent progestogen hormone replacement therapy (HRT) regimen to a continuous combined HRT regimen in postmenopausal women. METHODS: Subjects were randomly assigned to receive treatment with either constant 17beta-estradiol (E2), 1 mg, plus intermittent norgestimate (NGM) 90 microg (3 days off, 3 days on) (n=221) or E2 2 mg/norethisterone acetate (NETA) 1 mg (n=217) for 1 year. Treatments were evaluated based on the incidence of hot flushes and uterine bleeding. RESULTS: Both regimens had similar bleeding profiles and provided comparable vasomotor symptom relief. However, breast discomfort and edema were experienced by twice as many subjects who received E2/NETA. CONCLUSIONS: The constant E2/intermittent NGM regimen was well tolerated and possesses similar efficacy compared with a continuous combined E2/NETA regimen and may be considered whenever HRT without withdrawal bleeding is deemed appropriate.

A study of patients' expectations and satisfaction in Singapore hospitals.

In today's highly competitive healthcare environment, hospitals increasingly realise the need to focus on service quality as a means to improve their competitive position. Customer-based determinants and perceptions of service quality therefore play an important role when choosing a hospital. This paper attempts to determine the expectations and perceptions of patients through the use of a generic, internationally used market research technique called SERVQUAL. An analysis covering 252 patients revealed that there was an overall service quality gap between patients' expectations and perceptions. Thus, improvements are required across all the six dimensions, namely, tangibility, reliability, responsiveness, assurance, empathy and accessibility and affordability.

An audit of intrathecal morphine analgesia for non-obstetric postsurgical patients in an adult tertiary hospital.

We conducted a retrospective audit of adult non-obstetric patients who had received a single dose of intrathecal morphine for postoperative analgesia. These patients were predominantly admitted to a regular postsurgical ward with strict hourly nursing observations, treatment protocols in place and supervision by an Acute Pain Service for the first 24 hours after intrathecal morphine administration. A total of 409 cases were examined for sedation score, incidence of respiratory depression and other side-effects, admission to the high dependency or intensive care unit and opioid-tolerance. Respiratory depression was defined as requiring treatment with naloxone (implying a sedation score of 3 irrespective of respiratory rate), or a sedation score of 2 with a respiratory rate less than six breaths per minute. The patients were predominantly elderly (57.2% were over the age of 70 years) and 84.8% had undergone vascular surgery. Of the total of 409 cases, only one case of respiratory depression was observed. A total of 77 patients were admitted to high dependency or intensive care unit for various reasons including management of postsurgical complications and patient co-morbidities. Our findings suggest that elderly patients who receive intrathecal morphine analgesia can be safely managed in a regular postsurgical ward.

The mycological and molecular study of Hortaea werneckii isolated from blood and splenic abscess.

Hortaea werneckii is an environmental dematiaceous fungus found in the halophilic environment. It causes tinea nigra. We report the isolation of H. werneckii from blood and splenic abscess of two patients with acute myelomonocytic leukaemia. H. werneckii grew at room temperature but not at 37 degrees C, it was identified by biochemical tests, growth characteristics and the presence of conspicuous collarette intercalary on dividing yeast cells. The use of specific oligonucleotide primer Hor-F (5'-TGGACACCTTCA TAACTCTTG-3') and Hor-R (5'-TCACAACGCTTAGAGACGG-3') confirmed the two isolates were H. werneckii. The sequence for 281 nucleotide of HW299 and HW403 were 99% identical but differed only in one nucleotide. In vitro anti-fungal susceptibility testing showed that the isolates were resistant to amphotericin B and flucytosine.

Studies on the Malayan forest rat filaria, Breinlia booliati (Filarioidea: Onchocercidae): course of development in rat host.

The development of Breinlia booliati is described in its natural host, Rattus sabanus and in an inbred strain of laboratory albino rat. The growth of the parasite is similar in both the rat hosts. The third moult occurs between six-eight days and the final moult between 24-28 days. Larvae were recovered initially from the skin and carcass. After five weeks, developing stages were seen only in the thoracic and abdominal cavities, the site of development of the adult worms. Worms became sexually mature by 11-12 weeks and there was considerable growth in length of the female worms after this stage.

Gastrointestinal surgery in patients with ovarian cancer.

OBJECTIVES: The objectives were to assess indications for and outcome and morbidity of gastrointestinal surgery in patients with ovarian cancer. METHODS: We reviewed 364 patients with ovarian cancer who underwent a total of 491 operations including a gastrointestinal procedure over a 10-year period. The 491 operations comprised 180 primary surgical procedures (37%), 44 second-look laparotomies (9%), and 267 procedures for recurrence or palliation (54%). RESULTS: Debulking of disease was the indication for bowel surgery for 87, 45, and 62% of cases in the three groups, respectively. Bowel obstruction was an indication in 14% of patients at primary surgery and in 34% at secondary surgery (P < 0.05). Rectosigmoid resection was the most common bowel operation overall, particularly in the primary surgery group (65%). Colostomy was performed in 30% of the cases of rectosigmoid resection at primary surgery. Small-bowel resection was most common in the surgery for recurrence or palliation group. The blood transfusion rate was 79%. Febrile morbidity was the most common complication overall (29%), with no significant differences among groups. Four patients (0.8%) required reoperation for an abscess or anastomotic leak. Nineteen operations (3.9%) were followed by death within 30 days, with no significant differences among groups. A weighted Cox model estimated that 21, 42, and 11% of patients would be alive 5 years after primary surgery, second-look laparotomy, and surgery for recurrence or palliation, respectively (P = 0.01). CONCLUSION: Gastrointestinal surgery is frequently indicated during operations for ovarian cancer. Gynecologic cancer surgeons should be trained accordingly. Patients with possibly malignant ovarian masses should receive preoperative bowel preparation and be counseled that bowel surgery may be needed but colostomy is not frequently required.