A phase I study of binimetinib (MEK 162), a MEK inhibitor, plus carboplatin and pemetrexed chemotherapy in non-squamous non-small cell lung cancer.

INTRODUCTION: MEK inhibition is a potential therapeutic strategy in non-small cell lung cancer (NSCLC). This phase I study evaluates the MEK inhibitor binimetinib plus carboplatin and pemetrexed in stage IV non-squamous NSCLC patients (NCT02185690). METHODS: A standard 3 + 3 dose-escalation design was used. Binimetinib 30 mg BID (dose level 1 [DL1]) or 45 mg BID (dose level 2 [DL2]) was given with standard doses of carboplatin and pemetrexed using an intermittent dosing schedule. The primary outcome was determination of the recommended phase II dose (RP2D) and safety of binimetinib. Secondary outcomes included efficacy, pharmacokinetics, and an exploratory analysis of response based on mutation subtype. RESULTS: Thirteen patients (6 DL1, 7 DL2) were enrolled: 7 KRAS, 5 EGFR, and 1 NRAS mutation. The RP2D was binimetinib 30 mg BID. Eight patients (61.5%) had grade 3/4 adverse events, with dose limiting toxicities in 2 patients at DL2. Twelve patients were evaluated for response, with an investigator-assessed objective response rate (ORR) of 50% (95% CI 21.1%-78.9%; ORR 33.3% by independent-review, IR), and disease control rate 83.3% (95% CI 51.6%-97.9%). Median progression free survival (PFS) was 4.5 months (95% CI 2.6 months-NA), with a 6-month and 12-month PFS rate of 38.5% (95% CI 19.3%-76.5%) and 25.6% (95% CI 8.9%-73.6%), respectively. In an exploratory analysis, KRAS/NRAS-mutated patients had an ORR of 62.5% (ORR 37.5% by IR) vs. 25% in KRAS/NRAS wild-type patients. In MAP2K1-mutated patients, the ORR was 42.8%. CONCLUSION: The addition of binimetinib to carboplatin and pemetrexed appears to have manageable toxicity with evidence of activity in advanced non-squamous NSCLC.

The development of a strength-focused mutual support group for caretakers of children with cerebral palsy.

OBJECTIVE: To examine the efficacy of a strength-focused mutual support group for reducing stress and enhancing psychological well-being of the caretakers of children with cerebral palsy. METHODS: This pre- and post-intervention outcome study, conducted by Department of Orthopaedics and Traumatology, Duchess of Kent Children's Hospital, recruited 12 primary caretakers of children with cerebral palsy in Hong Kong. A strength-focused support group manual was developed to help such caretakers to identify and cultivate the character strengths of their children and enhance their own positive emotions. Participants were asked to complete a full set of questionnaires at 3 time-points: before and immediately after the intervention (consisting of 4 weekly sessions), and after the 1-month follow-up booster session. Two additional questionnaires were administered before each session to check mood. Parenting stress, anxiety, depression, social support, hope, and other psychological well-being measures were also assessed. RESULTS: Half of the caretakers (n = 6) who had attended the full intervention programme were included in the data analysis. Participants exhibited a significantly lower level of parental stress and higher hope level both after the 4 intervention sessions and at the booster session. Their perceived social support was significantly increased when the group was ongoing but not after it ended. CONCLUSION: This group intervention programme could effectively help caretakers reduce their parenting stress and enhance their hopefulness. Launching a similar programme with more sessions and regular follow-up sessions might help maintain positive effects and establish a social support network.

Right-lobe live donor liver transplantation improves survival of patients with acute liver failure.

BACKGROUND: Right-lobe live donor liver transplantation (LDLT) is used by many liver transplant centres for treating adult patients with terminal liver disease, but its incremental benefit for the intended recipient over cadaveric liver graft transplantation has not been determined. The impact of LDLT as a proactive approach on the outcome of patients with acute liver failure was analysed. METHODS: From January 1999 to March 2001, right-lobe LDLT was offered proactively to 50 consecutive patients with acute liver failure and their families. The outcome of those who opted for right-lobe LDLT (n = 34) was compared with that of those who did not opt for LDLT (n = 16). RESULTS: In the group that opted for right-lobe LDLT, 16 patients eventually received a live donor right-lobe graft (14 patients survived) and three patients received a cadaveric liver graft that became available while the potential live donor was undergoing evaluation (all three patients survived). Among the group who did not opt for LDLT, only one patient received a cadaveric liver graft and survived. The former group had a higher overall survival rate (17 of 34 versus one of 16). With a proactive approach, the overall transplant rate was increased from four of 50 to 20 of 50. The morbidity rate among donors was low and none died. CONCLUSION: Right-lobe LDLT improves the overall survival rate of patients with acute liver failure and should be considered as one of the treatment options for adult patients with acute liver failure.

Diffusion-weighted MR imaging of the liver: distinguishing hepatic abscess from cystic or necrotic tumor.

BACKGROUND: We evaluated the ability of diffusion-weighted (DW) magnetic resonance (MR) imaging to differentiate between hepatic abscess and cystic or necrotic liver tumor. METHODS: DW MR imaging was performed in 18 patients who had liver masses with large cystic or necrotic cavities detected by computed tomography or ultrasonography. The final diagnoses were pyogenic abscess (five cases), fungal abscess (one), hepatocellular carcinoma (five), cystic metastasis (four), and hepatic cyst (three). Signal intensities on the DW images and apparent diffusion coefficient (ADC) maps were noted. ADCs in all lesions were calculated and compared with Student's t test. RESULTS: All lesions, except hepatic cysts, showed either heterogeneous or homogeneous rim enhancement on postgadolinium images. All abscess cavities showed hyperintensity on DW images and hypointensity on ADC maps. Conversely, the cystic or necrotic portions of all tumors showed hypointensity on DW images and hyperintensity on ADC maps. The mean ADCs (mm(2)/s) were 0.67 +/- 0.35 x 10(-3) in hepatic abscess, 2.65 +/- 0.49 x 10(-3) in cystic or necrotic tumor, 2.93 +/- 0.52 x 10(-3) in hepatic cyst, and 1.98 +/- 0.37 x 10(-3) in normal liver parenchyma. CONCLUSION: DW MR imaging, with the help of ADCs, may be a useful noninvasive imaging technique in differentiating hepatic abscess from cystic or necrotic tumor.

Important role of cardiac spect imaging in patients undergoing percutaneous transluminal coronary angioplasty.

OBJECTIVE: To examine the utilization and contribution of cardiac perfusion scans to patients undergoing percutaneous transluminal coronary angioplasty. METHODS: From July 1996 to January 1998, 34 patients underwent percutaneous transluminal coronary angioplasty and cardiac SPECT imaging was studied. Twenty-five patients had pre-procedure SPECT scans. The agreement between angioplasty strategies and SPECT findings of ischemia and hypokinesia was examined. RESULTS: When radionuclide imaging was performed before revascularization procedures, 84% of the patients had intervention strategies guided by scan findings. Perfusion scan findings including extent and severity of ischemia, degree of hypokinesia directed the selection of target vessel for angioplasty in the patient subgroup with multi-vessel disease. Post-angioplasty radionuclide cardiac scans were performed only on symptomatic patients, demonstrating ischemia and hypokinesia in most of them, conceivably reflected the selection bias. CONCLUSION: We recommend routine pre- and post-angioplasty radionuclide imaging with multigated scans for wall motion assessment for all patients receiving coronary intervention.

The 15-year outcome of Chinese patients with schizophrenia in Hong Kong.

OBJECTIVE: To explore the differential outcome of schizophrenia in developed and developing countries. The 15-year outcome of patients with schizophrenia in Hong Kong is reported. METHOD: In a 15-year retrospective outcome study, 100 patients with first-onset schizophrenia in 1977-1978 were randomly selected for outcome assessment from a pool of 797 patient files. The patterns of outcome were assessed by the same set of instruments and methodology as in other centres, since Hong Kong is 1 of the World Health Organization (WHO) centres for the International Study of Schizophrenia (ISoS). RESULTS: Nineteen subjects were untraceable, and 10 subjects committed suicide. More than one-half of the subjects had a good symptomatic outcome, while about 20% of the subjects were rated as having a good psychosocial adjustment. Over the entire 15-year period, 96% of the subjects were maintained on medications, and 79% were living with family members. CONCLUSION: Despite Hong Kong's developed economy, its schizophrenia outcome is similar to that in developing countries. The existence of good family support and active follow-up treatment may be important contributory factors to better outcome.

Psychological interventions in general hospitals: background, current status and clinical guidelines.

PURPOSE: To promote the systematic development, interests, practice, research and clinical applications of health psychology in general hospitals in Hong Kong and the mainland of China. DATA SOURCES: The targets and aims of therapeutic work with patients in pain, cancer patients, child and adolescent patients, patients with chronic illnesses, the elderly, and patients requiring organ transplantation are highlighted. STUDY SELECTION: The psychological interventions described are experiences derived from routine clinical services carried out in the Clinical Health Psychology Unit where the authors are affiliated, and can be seen as an example of a more comprehensive psychological intervention program for physically ill patients in Hong Kong. RESULTS: Psychological interventions have intrinsic values in reducing patients' distress and sufferings. The services are also an integral part of modem day comprehensive patient care with positive effects on treatment effectiveness and eventual illness outcome. CONCLUSIONS: Physical illnesses affect a person physically as well as psychologically. Psychological care in general hospitals is cost effective and beneficial in reducing undue psychological complications precipitated by physical afflictions as well as in promoting better overall outcomes.

ERCP-induced acute necrotizing pancreatitis: is it a more severe disease?

Acute necrotizing pancreatitis (ANP) is an uncommon but serious complication of endoscopic retrograde cholangiopancreatography (ERCP). This study compares the severity, clinical course, and long-term outcome of ERCP-induced ANP with ANP induced by other causes. A review of 72 consecutive patients with ANP treated surgically at the Mayo Clinic identified ERCP as the cause in 6 patients (8%). Compared to the remaining 66 patients, the post-ERCP group had higher APACHE II scores on admission (mean, 13 vs. 10) and more extensive pancreatic necrosis (mean, 55 vs. 47%). The post-ERCP group had a higher rate of infected necrosis (100 vs. 75%) and required earlier necrosectomy after the onset of pancreatitis (9 vs. 13 days). The rate of postoperative pancreatic and enteric fistulae was also higher (50 vs. 33%). Although the mortality rate in the post-ERCP group was lower (17 vs. 29%), they were significantly younger (50 vs. 62 years; p = 0.02) and all the survivors had residual long-term morbidity. ANP is more severe when ERCP-induced; infection introduced during the ERCP may, in part, account for this severity.

Accuracy of current educational literature on the staging of gastric carcinoma.

Staging of gastric adenocarcinoma is important for comparing aspects of the disease in Asia and in the Western countries, and it may be used to direct the treatment strategy. A survey of 13 popular current surgical textbooks and review journals found a high level of inaccuracy. Two texts (15%) did not mention any staging systems, and one (8%) described a nonstandard system. Three (23%) described staging systems that were out of date, and six descriptions (46%) were inaccurate. Only 40% of the cited staging systems was reliable. This level of inaccuracy leads to confusion for the reader and to difficulty interpreting other relevant literature.

An episode of syncope attacks in adolescent schoolgirls: investigations, intervention and outcome.

An increasing number of students in a secondary convent girls school developed syncope attacks over a time course of about two months. Fourteen students who suffered from syncope and 12 other students from the same class with no symptoms were assessed by a team of psychologists and paediatricians with the aim of identifying the cause of the problem and to formulate possible remedial action. Psychological assessments included a mental state examination, developmental, personal and psychological history, state-trait anxiety, self-esteem, hypnotic suggestibility, and students' beliefs about the cause and nature of the syncope attacks. Physical investigations included physical examination, blood pressure and electrocardiogram. The results indicated that most participants and controls had no physical or psychological pathologies. The two groups were not different on the physical and psychological measures. Analyses of the interview data, however, indicated that all the syncope sufferers belonged to a cohesive and exclusive social network. Social psychological circumstances rather than individual psychopathology were noted to be primarily responsible for the spread and maintenance of the mass hysterical influence. Intervention consisted of health education, authoritative reassurance and back-up support. Follow-up assessment after three and 12 months indicated no further syncope episodes.

Pre-operative analgesia for acute surgical patients: no place for complacency.

Pain is common in patients presenting with acute surgical conditions but there has been little discussion of the provision of pre-operative analgesia. This study analyses the pattern of pre-operative analgesic administration and questions the practices of the admitting medical officers in a district hospital. It shows that pre-operative analgesia is often omitted or that an unduly long time is taken to administer it. We suggest that this is an area worthy of audit.