Response to sequential treatment with prednisolone and vigabatrin in infantile spasms.

AIM: To report response to first treatment in infants with infantile spasms (IS), including incremental benefit of prednisolone 60 mg/day and vigabatrin following prednisolone 40 mg/day failure in infants commenced on the United Kingdom Infantile Spasms Study (UKISS) treatment sequence. METHODS: In this retrospective analysis, we compared effectiveness of prednisolone, vigabatrin and nonstandard treatments as first treatment for IS. In infants who commenced the UKISS treatment sequence, we evaluated response to each step. Primary outcome was spasm cessation after 42 days. Secondary outcomes were severe side effects and spasm relapse after 42 days. RESULTS: Treatment response data were available for 151 infants. First treatment was prednisolone in 99 infants, vigabatrin in 18 and nonstandard treatment in 34. The rate of spasm cessation with first treatment was significantly higher with prednisolone (62/99, 63%) than vigabatrin (5/18, 28%, P = 0.01) or nonstandard treatment (2/34, 5.9%, P < 0.01). Of 112 infants who commenced the UKISS treatment sequence, 71/112 (63%) responded to prednisolone 40 mg/day. Among non-responders, 12/29 (41%) subsequently responded to prednisolone 60 mg/day, and 10/22 (45%) to vigabatrin. Severe side effects and spasm relapse were not significantly different between each treatment. CONCLUSION: We confirm higher rates of spasm cessation with initial treatment with prednisolone than vigabatrin and nonstandard therapy. Non-use of prednisolone as first treatment in over one third of infants highlights a concerning treatment gap. The UKISS treatment sequence has high overall treatment response (total 93/112; 83%), with similar benefit of subsequent prednisolone 60 mg/day and vigabatrin in prednisolone 40 mg/day non-responders.

The impact and cost-effectiveness of 9-valent human papillomavirus vaccine in adolescent females in Hong Kong.

INTRODUCTION: In Hong Kong (HK), a single-cohort vaccination program for 10-12-year-old girls with the 9-valent human papillomavirus (HPV) vaccine (9vHPV; types 6/11/16/18/31/33/45/52/58) has been launched. This study assessed the public health impact and cost-effectiveness of implementing routine 9vHPV vaccination (12-year-olds) with or without catch-up 9vHPV vaccination (13-18-year-olds) in HK. METHODS: The health impact and costs of implementing routine 9vHPV vaccination with or without catch-up vaccination over a 100-year time horizon were evaluated using a validated HPV-type transmission dynamic model adapted to the HK population; analyses were performed from a healthcare payer perspective. Routine vaccination (12-year-old girls) and catch-up vaccination (13-18 years) assumed vaccine coverage rates of 70% (base case) and 30%, respectively. The model also assumed herd immunity, lifelong vaccine protection, a discount rate of 3%, and a cost per dose of HK dollars (HKD) 858 [United States dollars (USD) 110] and HKD 1390 (USD 179) for the 2-valent HPV (2vHPV) and 9vHPV vaccines, respectively. HPV disease-related incidence and the incremental cost-effectiveness ratio (ICER) per quality-adjusted-life-year (QALY) were estimated. Cost-effectiveness was determined at a ceiling threshold of HK dollars (HKD) 382,046 (USD 49,142) or 1.0 times the gross domestic product per capita of HK. RESULTS: Compared with routine 9vHPV alone, routine plus catch-up 9vHPV is projected to reduce cervical cancer incidence by 3.4%. Routine plus catch-up 9vHPV will also reduce genital warts incident cases for males/females by 2.6%/5.4%. The incremental cost-effectiveness ratios were HKD 29,911 (USD 3847)/quality-adjusted life-year (QALY) for routine plus catch-up 9vHPV versus routine 9vHPV alone and HKD 25,524 (USD 3283)/QALY for routine 9vHPV alone versus screening only. Sensitivity analyses indicated that routine plus catch-up 9vHPV compared with routine 9vHPV alone remained cost-effective at coverage rates of 30% and 90%. CONCLUSIONS: This analysis predicts that the current HK vaccination strategy can be considered cost-effective and will provide maximum health benefit. These results support addition of the routine 9vHPV vaccine with or without catch-up 9vHPV vaccination to the regional vaccination program in HK.

Spontaneous resolution of posterior ankle joint loose bodies after total ankle replacement: A case report.

Late stage ankle osteoarthritis often presents with debilitating pain. It is common to find osteophytes and loose body formation around the joint. Total ankle arthroplasty can preserve joint mobility and pain relieve for such patient. However, when trying to remove the osteophytes and loose bodies at the posterior ankle joint, there is risk of damaging posterior structures such as the neurovascular bundle during the procedure. We are presenting a case where the posterior loose bodies remained untouched during the operation, and patient showed spontaneous resolution of the lesions with time. Patient enjoyed good function outcome after the surgery.

Effects of corticosterone and amyloid-beta on proteins essential for synaptic function: implications for depression and Alzheimer's disease.

The relationship between Alzheimer's disease (AD) and depression has been well established in terms of epidemiological and clinical observations. Depression has been considered to be both a symptom and risk factor of AD. Several genetic and neurobiological mechanisms have been described to underlie these two disorders. Despite the accumulating knowledge on this topic, the precise neuropathological mechanisms remain to be elucidated. In this study, we propose that synaptic degeneration plays an important role in the disease progression of depression and AD. Using primary culture of hippocampal neurons treated with oligomeric Aß and corticosterone as model agents for AD and depression, respectively, we found significant changes in the pre-synaptic vesicle proteins synaptophysin and synaptotagmin. We further investigated whether the observed protein changes affected synaptic functions. By using FM(®)4-64 fluorescent probe, we showed that synaptic functions were compromised in treated neurons. Our findings led us to investigate the involvement of protein degradation mechanisms in mediating the observed synaptic protein abnormalities, namely, the ubiquitin-proteasome system and autophagy. We found up-regulation of ubiquitin-mediated protein degradation, and the preferential signaling for the autophagic-lysosomal degradation pathway. Lastly, we investigated the neuroprotective role of different classes of antidepressants. Our findings demonstrated that the antidepressants Imipramine and Escitalopram were able to rescue the observed synaptic protein damage. In conclusion, our study shows that synaptic degeneration is an important common denominator underlying depression and AD, and alleviation of this pathology by antidepressants may be therapeutically beneficial.

Health impact and cost-effectiveness of implementing gender-neutral vaccination with the 9-valent HPV vaccine in Hong Kong.

Human papillomavirus (HPV) can cause several diseases, including cancers, in both sexes. In January 2020, the Hong Kong government launched a school-based vaccination program for girls 10-12 years of age with the 9-valent HPV (9vHPV) vaccine for the prevention of HPV-related diseases; however, boys were not included. The current study estimated the potential health and economic impact of a routine gender-neutral vaccination (GNV) approach compared with the current female-only vaccination (FOV) strategy. We used a dynamic transmission model, adapted to Hong Kong. The model estimates changes in HPV-related disease incidence and mortality, treatment costs (in 2019 Hong Kong dollars), quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICERs) over a 100-year time horizon. The base case analysis compared FOV with the 9vHPV vaccine with routine GNV (coverage rate 70%) for the prevention of HPV-related diseases. Compared with a FOV approach, routine GNV with the 9vHPV vaccine is predicted to provide greater reductions in cumulative HPV-related disease incidence and mortality, as well as lower HPV-related treatment costs. In the base case analysis, the ICER was $248,354 per QALY for routine GNV. As compared with FOV, routine GNV fell below the cost-effectiveness ceiling of $382,046/year for Hong Kong. These results highlight the potential value of a routine GNV program with the 9vHPV vaccine among 12-year-olds in Hong Kong to reduce the public health and economic burden of HPV-related diseases.

Factors affecting mortality in Hong Kong patients with upper limb necrotising fasciitis.

OBJECTIVE: To identify predictive factors for mortality of patients with upper limb necrotising fasciitis. DESIGN: Retrospective study. SETTING: Six hospitals in Hong Kong. PATIENTS: Clinical records of 29 patients treated in the hospitals were traced and analysed. MAIN OUTCOME MEASURES: Possible predictive factors for mortality as evaluated by application of Fisher's test. RESULTS: Overall mortality was 28%. Digital infections conferred a lower mortality, but progressive necrosis necessitated amputation. Vibrio vulnificus was the commonest organism identified in association with marine injury and in patients with cirrhosis. Prognostic indicators with decreasing significance include deranged renal and liver function, thrombocytopaenia, proximal involvement (elbow or above) initially, and presence of hypotension upon admission. CONCLUSION: With a P value of less than 0.05, deranged renal and liver function, thrombocytopaenia, initial proximal involvement, and hypotension on admission were predictors of mortality in necrotising fasciitis affecting the upper limbs. The ALERTS (Abnormal Liver function, Extent of infection, Renal impairment, Thrombocytopenia, and Shock) score with a cutoff of 3 appeared to predict mortality.

Do we need to repair the nerves when replanting distal finger amputations?

Distal replantation is an excellent model to study the results of nerve repair. We aim to demonstrate differences in aesthetic, sensory, and functional outcomes in fingertip replantation, with and without nerve repair. We recruited 28 fingers in 28 patients, who had successful distal replantation in 5 years. Half of the fingers had nerves repaired. Mean follow-up was 39 months. Symptoms of pain, numbness, cold intolerance, scar hypersensitivity, pulp atrophy, and weakness were reported. Nail width, pulp length, 2-point discrimination, Semmes-Weinstein test, and power were evaluated. We used chi-square tests of independence to examine association between nerve repair and symptoms, and independent T tests and Mann-Whitney U tests to analyze difference between replantation with and without nerve repair according to objective results. Chi-square tests reviewed no significant association between nerve repair and symptoms. Mann-Whitney U tests showed no significant difference between the groups, with and without nerve repair. All fingers showed mean 2-point discrimination of 5.6 mm, and Semmes-Weinstein test results of green in 3 fingers and blue in 17. There was no significant difference in overall outcomes in repairing nerve or not in distal finger replantation. Both groups had satisfactory outcomes. Possibly, spontaneous neurotization is present, and nerve repair is not necessary, which may help to shorten the operation time and decrease extensiveness of surgeries.

Cost-effectiveness of letermovir as cytomegalovirus prophylaxis in adult recipients of allogeneic hematopoietic stem cell transplantation in Hong Kong.

BACKGROUND: The cost-effectiveness of letermovir as cytomegalovirus (CMV) prophylaxis in adult seropositive patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT), compared with the conventional strategy of preemptive treatment, has not been evaluated in Asia. METHODS: A decision analytical model, simulating the clinical progression of CMV infection on a lifetime horizon, was developed to compare prophylactic strategy with letermovir with preemptive therapy alone as anti-CMV strategies. Prophylaxis comprised administering letermovir for 14 weeks, with clinical outcomes measured at 24 weeks, followed by preemptive therapy if CMV infection occurred. This approach was modeled on outcomes of the letermovir phase 3 clinical study. The model enumerated the cost of letermovir prophylaxis, quality-adjusted life years (QALYs), and incremental cost per QALYs gained with prophylaxis. The opposite arm involved regular monitoring and preemptive therapy for CMV reactivation. Real-world costs from the adult HSCT center at Queen Mary Hospital, Hong Kong, were adopted for analysis. Costs and clinical benefits, expressed as QALYs, were discounted at 3% per year. RESULTS: Letermovir prophylaxis compared with preemptive therapy only would lead to an increase of life-year and QALYs at increased costs. Incremental cost-effectiveness analysis showed that letermovir prophylaxis had an associated cost of HKD 193,580 for each life-year gained, and HKD 234,675 for each QALY gained. Probabilistic sensitivity analysis showed that the majority of incremental cost-effectiveness ratio fell below the cost-effectiveness threshold of HKD 382,046 (one gross domestic product per capita) per QALY gained. CONCLUSIONS: Letermovir prophylaxis would be cost-effective for preventing CMV infection in adult seropositive allogeneic HSCT recipients in Hong Kong.

In the Name of Family Medicine: A Nationwide Survey of Registered Names of Family Medicine Clinics in Taiwan.

Family medicine is officially a specialty, but is often not regarded as a specialty by the general public. Past studies have usually investigated the opinions of medical students and resident physicians regarding family medicine, whereas few have focused on practicing family physicians themselves, especially in terms of analyzing how they represent themselves. This study aimed to investigate the patterns of clinic names to better apprehend whether general practitioners see themselves as being on an equal footing with other medical specialists. The registered names, medical specialties, and levels of urbanization of all clinics of Western medicine in Taiwan were collected. For clinics of each specialty, we examined whether their names contained the corresponding specialty designation. For example, a family medicine clinic was checked to determine whether its name contained the term "family medicine" or its abbreviation. The naming of family medicine clinics was then compared with that of clinics with other specialties. Of the 9867 Western medicine clinics included in this study, two-thirds (n = 6592) were single-specialty clinics. In contrast to the high percentages of single-specialty clinics of other specialties with specialty-containing names (97.5% for ophthalmology, 94.8% for dermatology, and 94.7% for otolaryngology), only 13.3% (132/989) of the family medicine clinics had such names. In addition, the urban family medicine clinics had a higher proportion (15.2%, 74/487) of specialty-containing names than the suburban (12.6%, 44/349) and rural family medicine clinics (9.2%, 14/153). Overall, a low percentage of family medicine clinics in Taiwan included "family medicine" in their names. This issue of professional identity deserves further qualitative investigation.

Minimizing superficial thermal injury using bilateral cryogen spray cooling during laser reshaping of composite cartilage grafts.

Composite cartilage grafts were excised from New Zealand rabbit ears. Flat composite grafts (of cartilage and overlying skin graft on both surfaces) were obtained from each ear and cut into a rectangle measuring 50 mm by 25 mm (x by y) with an average thickness of approximately 1.3 mm (z), skin included. Specimens were manually deformed with a jig and maintained in this new position during laser illumination. The composite cartilage grafts were illuminated on the concave surface with an Nd:YAG laser (1,064 nm, 3 mm spot) at 10 W, 20 W, 30 W, 40 W, 50 W. Cryogen spray cooling (CSC) was applied to both exterior (convex) and interior (concave) surfaces of the tissue to reduce thermal injury to the grafts. CSC was delivered: (1) in controlled applications (cryogen released when surface reached 40 degrees C, and (2) receiving only laser at above wattage, no CSC [representing the control group]. The specimens were maintained in a deformation for 15 minutes after illumination and serially examined for 14 days. The control group with no CSC caused injury to all specimens, ranging from minor to full thickness epidermal thermal injury. Although most levels of laser and CSC yielded a high degree of reshaping over an acute time period, after 14 days specimens exposed to 30 W, 40 W, 50 W retained shape better than those treated at 10 W and 20 W. The specimens exposed to 50 W with controlled CSC retained its new shape to the highest degree over all others, and thermal injury was minimal. In conclusion, combinations of laser and CSC parameters were effective and practical for the reshaping of composite cartilage grafts.

A reciprocal relationship between reactive oxygen species and mitochondrial dynamics in neurodegeneration.

Mitochondrial fragmentation due to fission/fusion imbalance has often been linked to mitochondrial dysfunction and apoptosis in neurodegeneration. Conventionally, it is believed that once mitochondrial morphology shifts away from its physiological tubular form, mitochondria become defective and downstream apoptotic signaling pathways are triggered. However, our study shows that beta-amyloid (Aß) induces morphological changes in mitochondria where they become granular-shaped and are distinct from fragmented mitochondria in terms of both morphology and functions. Accumulation of mitochondrial reactive oxygen species triggers granular mitochondria formation, while mitoTEMPO (a mitochondria-targeted superoxide scavenger) restores tubular mitochondrial morphology within Aß-treated neurons. Interestingly, modulations of mitochondria fission and fusion by genetic and pharmacological tools attenuated not only the induction of granular mitochondria, but also mitochondrial superoxide levels in Aß-treated neurons. Our study shows a reciprocal relationship between mitochondrial dynamics and reactive oxygen species and provides a new potential therapeutic target at early stages of neurodegenerative disease pathogenesis.

Microvascular effects of Photofrin(®)-induced photodynamic therapy.

BACKGROUND AND OBJECTIVE: The object of our study is to evaluate the feasibility of photodynamic therapy (PDT) for complicated hemangiomas. The photosensitizing activities of Photofrin(®) have been used in vivo models for our goal of evaluation. STUDY DESIGN/MATERIALS AND METHODS: The in vivo biological activities of Photofrin(®) exposed to the total laser energy density of 100J/cm(2) with the power density of 100 or 120mW/cm(2) at 630nm wavelength was studied. The amount of vascular damage produced in the chick chorioallantoic membrane (CAM) was evaluated. At 630nm wavelength, those individual vessels with a diameter of 40µm or less and those with a diameter between 40 and 100µm were treated with Photofrin(®) at a concentration of about 2.5mg/mL, and injected intraperitoneally at 2.5mg/kg, illuminated at 100 and 120mW/cm(2), respectively. Both exhibited coagulation. RESULTS: There were no statistically significant differences between the two groups (100 and 120mW/cm(2)) on vessel damage grade 1. With vessel damage grades 2 and 3, the differences were statistically significant between two groups. Vessel damages between arterioles and venules also demonstrated differences in the 100mW/cm(2) treated group but not in the 120mW/cm(2) group. Statistically significant differences were also shown in arteriole and venules damage between 100 and 120mW/cm(2) treated groups. The severity of vessel damage between grades 1 and 2, 1 and 3, and 2 and 3, were compared. The differences were statistically significant in 100mW/cm(2) treated group. There was no statistically significant difference in 120mW/cm(2) treated group. CONCLUSION: Photofrin(®) has the capabilities for destruction of microvascular vessels of CAM. Extension of this study to the second-generation photosensitizers is underway. The most important treatment variables seem to be the power density.

Investigating degeneration of the retina in young and aged tau P301L mice.

AIMS: Tau is a microtubule-binding protein facilitating the stability of the cytoskeleton. It is important for neurons as several neurodegenerative diseases involve hyperphosphorylation and aggregation of tau. It is known that mutated tau P301L results in aggregation of tau proteins, leading to neuronal loss in the brain. The aim of this study was to investigate the effect of tau mutation on the retina using a transgenic tau P301L mouse model. MAIN METHODS: Morphometric analysis was utilized to quantify the neurodegenerative changes, including the thickness of the inner nuclear layer (INL), and the density and size of retinal ganglion cells (RGCs). Sections of retina tissue stained by hematoxylin and eosin (H&E) and immunohistochemistry were analyzed. Comparisons were made between the tau P301L mice and control mice, as well as between different age groups. KEY FINDINGS: A significant decrease in the thickness of the INL in tau P301L mice was found when compared with that of control mice. The effect was more pronounced in the peripheral area, and the effect increased with age. Regarding density of RGCs, tau P301L mice showed a similar age-related decline as in control mice. Furthermore, the RGCs from tau P301L mice increased in size with age, and the RGCs from control mice decreased in size with age. SIGNIFICANCE: Tau may be an age-independent factor of accelerated neurodegeneration, with effects differing by types of neurons and regions of the retina.

Wrist Arthroscopy under Portal Site Local Anesthesia (PSLA) without Tourniquet.

UNLABELLED: Purpose wrist arthroscopy is typically performed under general or regional anesthesia with the aid of a tourniquet to maintain a bloodless field. We have been using portal site local anesthesia (PSLA) for wrist arthroscopy without a tourniquet since 1998. The aim of the study was to assess the efficacy, safety, and complications of PSLA and whether this can be recommended for routine wrist arthroscopy. Method We conducted a retrospective study, identifying 111 consecutive cases of wrist arthroscopies performed from January 2007 to December 2009. All cases were performed under PSLA. The effectiveness of PSLA was assessed by analyzing whether the procedure required adjuvant forms of anesthesia. The subjective effectiveness was assessed via phone questionnaires. Results Sixty-eight male and 43 female patients were identified. The average age was 43.2 (range 16-77). The indications included chronic wrist pain of unknown origin (30), posttraumatic arthritis (27), rheumatoid arthritis (5), ganglion (30), triangular fibrocartilage complex (TFCC) injury (14), infectious (1), and carpal instability (4). The average duration of the procedures was 73 minutes (range 20-255 minutes). Therapeutic procedures were performed in all 111 cases in addition to a routine diagnostic assessment. These included arthroscopic debridement (82) synovectomy (6), ganglionectomy (30), TFCC repair (3), TFCC debridement (11), radial styloidectomy (2), wafer procedure (4), thermal shrinkage (2), distal scaphoidectomy (1), and synovial biopsy (4). All procedures could be completed uneventfully. Most patients tolerated the procedure well throughout the operation, and the satisfaction level was high. No complication was encountered. Discussions We concluded that PSLA technique is a feasible mode of anesthesia in selected patients. LEVEL OF EVIDENCE: Level IV.

Health-related quality of life of children with epilepsy in Hong Kong: how does it compare with that of youth with epilepsy in Canada?

OBJECTIVE: The primary aim of our study was to compare the health-related quality of life (HRQL) of children with epilepsy in Hong Kong with that of children with epilepsy in Canada, and to explore possible factors affecting these findings. A second interest was to determine agreement between proxy reports and self-ratings among children with epilepsy in Hong Kong, compare these with findings in Canada, and identify factors that influence the concordance. METHODS: Child self-report and parent-proxy questionnaires on an epilepsy-specific HRQL measure, appropriately translated and validated in Chinese, were administered to 266 Hong Kong children and their parents. An unpaired t test was used to compare the scores with published results from 381 Canadian children and their parents, who used the original English version of the measure. Demographic characteristics of the two groups were compared using t tests, chi2 tests, and Fisher's exact tests. Agreement between parents' and children's scores was evaluated with intraclass correlation coefficients (ICCs) and standardized response means (SRMs). The total HRQL score differences between parents and children in Hong Kong were compared with those in Canada using an unpaired t test. Factors that might affect the parent-child score difference were studied using Pearson correlation analysis, chi2 test, and analysis of variance. Factors studied included: sex, current age, age at diagnosis, duration of epilepsy, number of antiepileptic drugs used, type of seizure, seizure severity, cognition of the child, the type of school attended, presence of neurological problems, presence of behavioral problems, recent health care usage, education and employment status of both parents, housing status of the family, and relationship of the proxy respondent to the child. RESULTS: (1) In contrast to the Canadian sample, Hong Kong children with epilepsy were older (P<0.01), had a longer duration of epilepsy (P<0.01) and less severe seizures (P<0.01), and were more likely to attend normal schools (P<0.01). Children in Hong Kong reported more interpersonal/social difficulties (P<0.01), more worries (P<0.01), and more secrecy about their epilepsy (P<0.01). Parents in Hong Kong believed that their children perceived more worries (P<0.01) and were more secretive about their epilepsy (P<0.01). (2) Moderate to good agreement between parent-proxy response scores and child self-report scores was demonstrated (ICC=0.50-0.69, SRM=0.19-0.33). The total HRQL score differences between parent and child in Hong Kong were not different from those in Canada. None of the factors studied were related to the parent-child score difference. CONCLUSIONS: Youth with epilepsy in Hong Kong and their parents reported poorer quality of life than children with epilepsy in Canada. Further studies are necessary to identify the determinants of HRQL in children with epilepsy in different cultures. Acceptable agreement between the two ratings suggests that proxy reports can be used when child self-reports cannot be obtained.