Consensus recommendations for the screening, diagnosis, and management of Helicobacter pylori infection in Hong Kong.

Helicobacter pylori infection causes chronic gastric inflammation that contributes to various gastroduodenal diseases, including peptic ulcer and gastric cancer. Despite broad regional variations, the prevalence of resistance to antibiotics used to manage H pylori infection is increasing worldwide; this trend could hinder the success of eradication therapy. To increase awareness of H pylori and improve the diagnosis and treatment of its infection in Hong Kong, our consensus panel proposed a set of guidance statements for disease management. We conducted a comprehensive review of literature published during 2011 and 2021, with a focus on articles from Hong Kong or other regions of China. We evaluated the evidence using the Oxford Centre for Evidence-Based Medicine's 2011 Levels of Evidence and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system and sought consensus through online voting and a subsequent face-to-face meeting, which enabled us to develop and refine the guidance statements. This report consists of 24 statements regarding the epidemiology and burden, screening and diagnosis, and treatment of H pylori. Key guidance statements include a recommendation to use the test-and-treat approach for high-risk individuals, as well as the confirmation that triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin remains a valid first-line option for adults and children in Hong Kong.

A systematic review and computational modelling analysis of unilateral montages in electroconvulsive therapy.

OBJECTIVE: To examine the clinical outcomes of ECT unilateral placements compared in prior studies and apply insights from computational modelling to understand differences between placements. METHODS: PubMed, Embase, Scopus and PsycINFO and reference lists were systematically searched for studies of depressed patients where two unilateral placements were compared and clinical outcomes were reported. Computational modelling was done to generate electric field maps for each unilateral placement identified in the systematic review. RESULTS: A total of 29 studies met criteria for inclusion. Eight studies reported efficacy outcomes and 23 studies reported cognitive outcomes. Most studies found no significant difference in efficacy between right unilateral (RUL) and left unilateral (LUL) ECT, and no difference was found between temporo-parietal and fronto-temporal ECT. For the majority of studies, RUL placements had better verbal anterograde memory outcomes compared with the LUL placements. There was some evidence suggestive of cognitive advantages for fronto-frontal and fronto-parietal placements relative to temporo-parietal ECT. CONCLUSIONS: For efficacy, studies mainly focused on the comparison of right vs. left hemispheric stimulation, with the available evidence suggesting no substantive difference. RUL placements tended to have better verbal anterograde memory outcomes relative to LUL placements, though limited differences were found between the RUL placements.

Placebo-controlled pilot trial testing dose titration and intravenous, intramuscular and subcutaneous routes for ketamine in depression.

OBJECTIVE: This pilot study assessed the feasibility, efficacy and safety of an individual dose-titration approach, and of the intravenous (IV), intramuscular (IM) and subcutaneous (SC) routes for treating depression with ketamine. METHOD: Fifteen treatment-refractory depressed participants received ketamine or midazolam (control treatment) in a multiple crossover, double-blind study. Ketamine was administered by IV (n = 4), IM (n = 5) or SC (n = 6) injection. Dose titration commenced at 0.1 mg/kg, increasing by 0.1 mg/kg up to 0.5 mg/kg, given in separate treatment sessions separated by ≥1 week, with one placebo control treatment randomly inserted. Mood, psychotomimetic and hemodynamic effects were assessed and plasma ketamine concentrations assayed. RESULTS: Twelve participants achieved response and remission criteria, achieved at doses as low as 0.1 mg/kg. All three routes of administration resulted in comparable antidepressant effects. Fewest adverse effects were noted with the SC route. Antidepressant response, adverse effects and ketamine concentrations were dose-related. CONCLUSION: Antidepressant response occurred at a range of doses and at <0.5 mg/kg. The dose-titration approach is a practical method for optimizing the efficacy - side-effects trade-off on an individual patient basis. This pilot study provides preliminary evidence for SC injection as a practical, feasible and efficacious treatment approach.

An outbreak of refrigerant-induced acute hepatitis in Hong Kong.

We report a cluster of acute hepatitis in five air-conditioning maintenance workers following accidental exposure to 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123). They presented to us with complaints of feverishness, generalised malaise, and epigastric discomfort. Their blood biochemistry tests were compatible with acute hepatitis. Viral hepatitis serology, tests for autoimmune hepatitis, and analyses for drugs and alcohol consumption were all negative. No focal hepatic lesion was detected by ultrasound imaging. Percutaneous liver biopsy samples were taken from two of them. The patients were managed with supportive treatment. All had spontaneous, but slow, recovery. Their liver function tests returned to normal after 4 months and their outcomes were favourable. Physicians should be aware of this occupational disease entity.

Transcranial direct current stimulation in the treatment of major depression: a meta-analysis.

BACKGROUND: So far, no comprehensive answer has emerged to the question of whether transcranial direct current stimulation (tDCS) can make a clinically useful contribution to the treatment of major depression. We aim to present a systematic review and meta-analysis of tDCS in the treatment of depression. METHOD: Medline and Embase were searched for open-label and randomized controlled trials of tDCS in depression using the expressions ('transcranial direct current stimulation' or 'tDCS') and ('depression' or 'depressed'). Study data were extracted with a standardized data sheet. For randomized controlled trials, effect size (Hedges' g) was calculated and the relationships between study variables and effect size explored using meta-regression. RESULTS: A total of 108 citations were screened and 10 studies included in the systematic review. Six randomized controlled trials were included in the meta-analysis, with a cumulative sample of 96 active and 80 sham tDCS courses. Active tDCS was found to be more effective than sham tDCS for the reduction of depression severity (Hedges' g=0.743, 95% confidence interval 0.21-1.27), although study results differed more than expected by chance (Q=15.52, df=6, p=0.017, I2=61.35). Meta-regression did not reveal any significant correlations. CONCLUSIONS: Our study was limited by the small number of studies included, which often had small sample size. Future studies should use larger, if possible representative, health service patient samples, and optimized protocols to evaluate the efficacy of tDCS in the treatment of depression further.

The utility of the Sydney Melancholia Prototype Index (SMPI) for predicting response to electroconvulsive therapy in depression: A CARE Network study.

An enhanced understanding of clinical predictors of positive ECT outcome could assist with the decision to prescribe ECT for select patients. Reliable predictors of ECT response such as psychotic symptoms and age have been identified, however, studies of melancholia and ECT response have been inconsistent. The Sydney Melancholia Prototype Index (SMPI) is a clinical measure designed to differentiate melancholic and non-melancholic depression. This study aimed to investigate whether melancholic depression (as measured by the clinician rated version of the SMPI) predicted a better response to ECT than non-melancholic depression. The study included data collated from four participating sites in the Clinical Alliance for ECT and Related treatments (CARE) network. The primary outcome was response (>50% improvement) on the Montgomery Asberg Depression Rating Scale (MADRS) and the secondary outcome was raw change in MADRS score. Of the 329 depressed patients included in the study, 81% had melancholic features and 76% met criteria for clinical response. SMPI defined melancholia was associated with older age, higher pre-treatment mood scores and presence of psychosis. Melancholia as defined by the SMPI, however, did not significantly predict either clinical response or overall mood improvement with ECT in multivariate analyses. Instead, older age, greater pre-treatment depression severity and the use of bifrontal compared to right unilateral ultrabrief ECT were significant predictors of mood improvement. Path analysis showed that higher pre-treatment mood score and older age were independently associated with mood improvement with ECT.

The utility of the brief ECT cognitive screen (BECS) for early prediction of cognitive adverse effects from ECT: A CARE network study.

Although highly effective, electroconvulsive therapy (ECT) often produces cognitive side effects which can be a barrier for patients. Monitoring cognitive side effects during the acute course is therefore recommended to identify patients at increased risk for adverse outcomes. The Brief ECT Cognitive Screen (BECS) is a brief instrument designed to measure emerging cognitive side effects from ECT. The aim of this study was to examine the clinical utility of the BECS for predicting adverse cognitive outcomes in real world clinic settings. The study included data collated from four participating sites in the Clinical Alliance for ECT and Related treatments (CARE) network. The BECS was administered at pre ECT and post 3 or 4 ECT. The primary outcome was a ≥4 point decrease on the Montreal Cognitive Assessment (MoCA) from pretreatment to post ECT. Logistic multiple regression analyses examined the BECS and other relevant clinical and demographic and treatment factors as predictors. The final analysis included 623 patients with diverse indications for ECT including 53.6% with major depression and 33.7% with schizophrenia or schizoaffective disorder. A higher total score on the BECS significantly predicted decline in Total Scores on the MoCA [B = 0.25 (0.08), p = 0.003], though not decline in MoCA Delayed Recall scores (p > 0.1). Other significant predictors included higher pretreatment MoCA Total Scores and female gender for verbal anterograde memory decline. This study confirmed that the BECS has clinical utility for identifying patients with both reduced and increased risk for adverse cognitive outcomes from ECT.

A sham-controlled trial of left and right temporal rTMS for the treatment of auditory hallucinations.

BACKGROUND: Several studies have reported reduction of auditory hallucinations (AH) after repetitive transcranial magnetic stimulation (rTMS) to the left temporal cortex. This study explored the effects of rTMS to the left and right temporal cortex. METHOD: Eighteen subjects with schizophrenia and frequent AH were enrolled in a double-blind, cross-over trial of 3 days of active rTMS to the left or right temporal cortex, or sham rTMS to the vertex (control condition), followed by an open treatment phase. The effects on AH were assessed by a blinded rater, using the Auditory Hallucination Rating Scale (AHRS). RESULTS: During the double-blind phase, active temporal rTMS did not result in significantly greater improvement in hallucination scores than sham rTMS to the vertex, apart from a reduction in distress scores. Hallucination scores improved during the open continued treatment phase. CONCLUSIONS: This study did not demonstrate an advantage for left temporal rTMS compared to right temporal and sham stimulation, over a 3-day stimulation period, but found modest improvement in hallucinations during continued open label treatment.

Clinical pilot study of transcranial direct current stimulation combined with Cognitive Emotional Training for medication resistant depression.

BACKGROUND: While the clinical results from transcranial direct current stimulation (tDCS) for the treatment of depression have been promising, antidepressant effects in patients with medication resistance have been suboptimal. There is therefore a need to further optimise tDCS for medication resistant patients. In this clinical pilot study we examined the feasibility, safety, and clinical efficacy of combining tDCS with a psychological intervention which targets dysfunctional circuitry related to emotion regulation in depression, Cognitive Emotional Training (CET). METHODS: tDCS was administered during CET three times a week for a total of 18 sessions over 6 weeks. Mood, cognition and emotion processing outcomes were examined at baseline and after 3 and 6 weeks of treatment. RESULTS: Twenty patients with medication resistant depression participated, of whom 17 were study completers. tDCS combined with CET was found to be feasible, safe, and associated with significant antidepressant efficacy at 6 weeks, with 41% of study completers showing treatment response (≥ 50% improvement in depression score). There were no significant cognitive enhancing effects with the exception of improved emotion recognition. Responders demonstrated superior recognition for the emotions fear and surprise at pre-treatment compared to non-responders, suggesting that better pre-treatment emotion recognition may be associated with antidepressant efficacy. LIMITATIONS: This was an open label study. CONCLUSIONS: tDCS combined with CET has potential as a novel method for optimising the antidepressant efficacy of tDCS in medication resistant patients. Future controlled studies are required to determine whether tDCS combined with CET has greater antidepressant efficacy compared to either intervention alone.

Association between neighbourhood walkability and metabolic risk factors influenced by physical activity: a cross-sectional study of adults in Toronto, Canada.

OBJECTIVE: To determine whether neighbourhood walkability is associated with clinical measures of obesity, hypertension, diabetes and dyslipidaemia in an urban adult population. DESIGN: Observational cross-sectional study. SETTING: Urban primary care patients. PARTICIPANTS: 78 023 Toronto residents, aged 18 years and over, who were formally rostered or had at least 2 visits between 2012 and 2014 with a primary care physician participating in the University of Toronto Practice Based Research Network (UTOPIAN), within the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). MAIN OUTCOME MEASURES: Differences in average body mass index (BMI), systolic and diastolic blood pressure, fasting blood glucose, haemoglobin A1c (HbA1C), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein and triglyceride between residents in the highest versus the lowest quartile of neighbourhood walkability, as estimated using multivariable linear regression models and stratified by age. Outcomes were objectively measured and were retrieved from primary care electronic medical records. Models adjusted for age, sex, smoking, medications, medical comorbidities and indices of neighbourhood safety and marginalisation. RESULTS: Compared with those in the lowest walkability quartile, individuals in the highest quartile had lower mean BMI (-2.64 kg/m2, 95% CI -2.98 to -2.30; p<0.001), systolic blood pressure (-1.35 mm Hg, 95% CI -2.01 to -0.70; p<0.001), diastolic blood pressure (-0.60 mm Hg, 95% CI 1.06 to -0.14; p=0.010) and HbA1c (-0.063%, 95% CI -0.11 to -0.021; p=0.003) and higher mean HDL (0.052 mmol/L, 95% CI 0.029 to 0.075; p<0.001). In age-stratified analyses, differences in the mean BMI were consistently observed for adults aged 18 to under 40 (-4.44 kg/m2, 95% CI -5.09 to -3.79; p<0.001), adults aged 40-65 (-2.74 kg/m2, 95% CI -3.24 to -2.23; p<0.001) and adults aged over 65 (-0.87 kg/m2, 95% CI -1.48 to -0.26; p=0.005). CONCLUSIONS: There was a clinically meaningful association between living in the most walkable neighbourhoods and having lower BMI in adults of all ages.

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines.

Low intensity transcranial electrical stimulation (TES) in humans, encompassing transcranial direct current (tDCS), transcutaneous spinal Direct Current Stimulation (tsDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation or their combinations, appears to be safe. No serious adverse events (SAEs) have been reported so far in over 18,000 sessions administered to healthy subjects, neurological and psychiatric patients, as summarized here. Moderate adverse events (AEs), as defined by the necessity to intervene, are rare, and include skin burns with tDCS due to suboptimal electrode-skin contact. Very rarely mania or hypomania was induced in patients with depression (11 documented cases), yet a causal relationship is difficult to prove because of the low incidence rate and limited numbers of subjects in controlled trials. Mild AEs (MAEs) include headache and fatigue following stimulation as well as prickling and burning sensations occurring during tDCS at peak-to-baseline intensities of 1-2mA and during tACS at higher peak-to-peak intensities above 2mA. The prevalence of published AEs is different in studies specifically assessing AEs vs. those not assessing them, being higher in the former. AEs are frequently reported by individuals receiving placebo stimulation. The profile of AEs in terms of frequency, magnitude and type is comparable in healthy and clinical populations, and this is also the case for more vulnerable populations, such as children, elderly persons, or pregnant women. Combined interventions (e.g., co-application of drugs, electrophysiological measurements, neuroimaging) were not associated with further safety issues. Safety is established for low-intensity 'conventional' TES defined as <4mA, up to 60min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3-13A/m2 that are over an order of magnitude above those produced by tDCS in humans. Using AC stimulation fewer AEs were reported compared to DC. In specific paradigms with amplitudes of up to 10mA, frequencies in the kHz range appear to be safe. In this paper we provide structured interviews and recommend their use in future controlled studies, in particular when trying to extend the parameters applied. We also discuss recent regulatory issues, reporting practices and ethical issues. These recommendations achieved consensus in a meeting, which took place in Göttingen, Germany, on September 6-7, 2016 and were refined thereafter by email correspondence.

Regulatory Considerations for the Clinical and Research Use of Transcranial Direct Current Stimulation (tDCS): review and recommendations from an expert panel.

The field of transcranial electrical stimulation (tES) has experienced significant growth in the past 15 years. One of the tES techniques leading this increased interest is transcranial direct current stimulation (tDCS). Significant research efforts have been devoted to determining the clinical potential of tDCS in humans. Despite the promising results obtained with tDCS in basic and clinical neuroscience, further progress has been impeded by a lack of clarity on international regulatory pathways. We therefore convened a group of research and clinician experts on tDCS to review the research and clinical use of tDCS. In this report, we review the regulatory status of tDCS, and we summarize the results according to research, off-label and compassionate use of tDCS in the following countries: Australia, Brazil, France, Germany, India, Iran, Italy, Portugal, South Korea, Taiwan and United States. Research use, off label treatment and compassionate use of tDCS are employed in most of the countries reviewed in this study. It is critical that a global or local effort is organized to pursue definite evidence to either approve and regulate or restrict the use of tDCS in clinical practice on the basis of adequate randomized controlled treatment trials.

Transcranial magnetic stimulation (TMS) in controlled treatment studies: are some "sham" forms active?

BACKGROUND: Carefully designed controlled studies are essential in further evaluating the therapeutic efficacy of transcranial magnetic stimulation (TMS) in psychiatric disorders. A major methodological concern is the design of the "sham" control for TMS. An ideal sham would produce negligible cortical stimulation in conjunction with a scalp sensation akin to real treatment. Strategies employed so far include alterations in the position of the stimulating coil, but there has been little systematic study of their validity. In this study, we investigated the effects of different coil positions on cortical activation and scalp sensation. METHODS: In nine normal subjects, single TMS pulses were administered at a range of intensities with a "figure eight" coil held in various positions over the left primary motor cortex. Responses were measured as motor-evoked potentials in the right first dorsal interosseus muscle. Scalp sensation to TMS with the coil in various positions over the prefrontal area was also assessed. RESULTS: None of the coil positions studied met the criteria for an ideal sham. Arrangements associated with a higher likelihood of scalp sensation were also more likely to stimulate the cortex. CONCLUSIONS: The choice of a sham for TMS involves a trade-off between effective blinding and truly inactive "stimulation." Further research is needed to develop the best sham condition for a range of applications.

Right versus left prefrontal transcranial magnetic stimulation for obsessive-compulsive disorder: a preliminary investigation.

BACKGROUND: There is preliminary evidence that repetitive transcranial magnetic stimulation (rTMS) may be useful for the treatment of obsessive-compulsive disorder (OCD), but no definitive study has been published, and the effect of laterality of stimulation is uncertain. METHOD: Subjects (N = 12) with resistant OCD were allocated randomly to either right or left prefrontal rTMS daily for 2 weeks and were assessed by an independent rater at 1 and 2 weeks and 1 month later. RESULTS: Subjects had an overall significant improvement in the obsessions (p < .01), compulsions (p < .01), and total (p < .01) scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) after 2 weeks and at 1-month follow-up. This improvement was significant for obsessions (p < .05) and tended to significance for total Y-BOCS scores (p = .06) after correction for changes in depression scores on the Montgomery-Asberg Depression Rating Scale. There was no significant difference between right- and left-sided rTMS on any of the parameters examined. Two subjects (33%) in each group showed a clinically significant improvement that persisted at I month but with relapse later in I subject. CONCLUSION: A proportion (about one quarter) of patients with resistant OCD appear to respond to rTMS to either prefrontal lobe, although in the absence of a sham treatment group in this study, we cannot rule out the possibility of this being a placebo response. This treatment warrants further investigation to better establish its efficacy and examine the best parameters for response.

Proprioceptive contributions to tactile identification of figures: dependence on figure size.

Studies on the recognition of objects or shapes explored by a hand or finger have concentrated on the relative merits of different methods of exploration--in particular, whether the exploring hand or finger is moved by the subject himself (active), is guided by an assistant (passive), or remains stationary with the shape being moved by an assistant (tactile). These factors, together with another variable--the size of the explored shape--were investigated in twelve normal adults whose task, without the aid of vision, was to explore and identify various shapes with the tip of the extended right index finger. Two series of shapes were used, a large (15 cm) and small (3 cm) series, both of which consisted of twelve shapes each being a variant of the letter 'S'. The shapes were outlined as rows of Braille-like dots on a flat surface. Exploration was also tested in the proprioceptive mode, in which the exploring hand was guided by an assistant around a shape which was simply drawn on the surface so as to give a minimum of tactile information. For neither large nor small shapes could we demonstrate differences between active, passive and proprioceptive exploration. For the small shapes, the active, passive and proprioceptive modes gave no advantage over purely tactile assessment. However, for the larger shapes, active, passive and proprioceptive modes allowed better identification than movement of the shape. Thus, purely cutaneous signals appear sufficient for optimal discrimination of small figures but proprioceptive signals, generated by movement, are needed for optimal discrimination of larger figures.

Intestinal obstruction and gastrointestinal bleeding due to systemic amyloidosis in a woman with occult plasma cell dyscrasia.

A 60-year-old woman presented to our hospital with repeated vomiting. Upper gastrointestinal endoscopy revealed a 1 cm diameter ulcer with clean base on the roof of the gastric antrum. Histological examination of gastric biopsies revealed abundant amorphous eosinophilic deposits in the submucosa. Congo red stain for amyloid was positive. A barium follow-through study revealed a mass in the jejunum causing incomplete obstruction. Urine for Bence Jones protein was negative. Serum protein electrophoresis did not reveal any abnormal band and serum immunoelectrophoresis did not detect any monoclonal immunoglobulin. Bone marrow examination, however, revealed an increased proportion of plasma cells. Subsequent immunohistochemical staining demonstrated monoclonal lambda light chains in the marrow plasma cells, thereby confirming a plasma cell dyscrasia. Amyloidosis involving the gastrointestinal tract can produce a wide variety of non-specific symptoms and signs. A high index of suspicion is necessary to arrive at an early diagnosis. Management consists of supportive therapy for the gastrointestinal tract as well as treatment of the underlying condition.

CNS findings in iniencephaly: case report and literature review.

A male iniencephalic foetus of about 25 weeks gestation is described. The baby was born to a 22-year-old mother, who presented with abdominal pain of 1 day duration. An ultrasound scan at that time showed multiple foetal anomalies and the pregnancy was terminated. A stillborn baby was delivered. At autopsy, characteristic findings of iniencephaly were seen in the dysmorphic foetus as well as multiple structural abnormalities. The autopsy results, with emphasis on the neuropathological findings, are described and various hypotheses of the pathogenesis of iniencephaly are discussed with reference to theories of embryological development and other cases in the literature.