A systematic review of community pharmacy interventions to improve peri- and post-menopausal health.

Menopause is defined as the permanent cessation of menstruation due to loss of ovarian follicular function. Symptoms include mood disorders, vaginal atrophy, hot flashes and night sweats and can emerge during a gradual transition period called perimenopause. Community pharmacies are well placed to deliver a wide range of healthcare services, including supporting and educating menopausal women; however, to date, no systematic review has assessed the effectiveness of community pharmacy-led interventions in improving peri- and post-menopausal health. In accordance with PRISMA guidelines we evaluated community pharmacy-led interventions that targeted women in peri- or post-menopause. Electronic searches in EMBASE, MEDLINE, CINAHL and Cochrane Library were conducted on 13th February 2023. Additionally, we examined the included studies references and citation lists using Google Scholar. A total of 915 articles were identified and screened against the inclusion criteria. Two studies were included; one identified post-menopausal women at risk of developing osteoporosis (OP), and one evaluated the outcomes of a community pharmacy-based menopause education programme. Study one found 11 (11%) post-menopausal women were at risk of developing OP based on quantitative ultrasound screening offered by community pharmacists and referred to their physician. Study two reported that women had access to adequate personalised menopause counselling and increased knowledge of menopause topics because of the educational programme within community pharmacies. Both studies were of low quality. The lack of included studies reflects the need for high-quality research to determine whether community pharmacy-led interventions are feasible, effective and acceptable, to improve health outcomes of peri- or post-menopausal women.

Rationale and methods for a cross-sectional study of mental health and wellbeing following river flooding in rural Australia, using a community-academic partnership approach.

BACKGROUND: Climate change is associated with greater frequency, duration, intensity and unpredictability of certain weather-related events, including floods. Floods harm mental health. There is limited understanding of the mental health and well-being effects from river flooding, particularly over the longer term and in rural contexts. This paper describes the rationale, aims, objectives, study design and socio-demographic characteristics of the sample for a study measuring associations between flood experience and mental health and wellbeing of residents (particularly those most likely to be negatively impacted and hard to reach) in rural NSW Australia 6 months following a devastating flood in 2017. To our knowledge, the study is the first of its kind within Australia in a rural community and is an important initiative given the likelihood of an increasing frequency of severe flooding in Australia given climate change. METHODS: A conceptual framework (The Flood Impact Framework) drawing on social ecological approaches was developed by the research team. It was based on the literature and feedback from the community. The Framework describes putative relationships between flood exposure and mental health and wellbeing outcomes. Within a community-academic partnership approach, a cross-sectional survey was then undertaken to quantify and further explore these relationships. RESULTS: The cross-sectional survey was conducted online (including on mobile phone) and on paper between September and November 2017 and recruited 2530 respondents. Of those, 2180 provided complete demographic data, among whom 69% were women, 91% were aged 25-74, 4% identified as Aboriginal and/or Torres Strait Islander, 9% were farmers and 33% were business owners. CONCLUSIONS: The study recruited a wide range of respondents and the partnership facilitated the community's engagement with the design and implementation of the study. The study will provide a basis for a follow-up study, that will aim to improve the understanding of mental health and wellbeing effects over the longer term. It will provide an important and original contribution to understanding river flooding and mental health in rural Australia, a topic that will grow in importance in the context of human-induced climate change, and identify critical opportunities to strengthen services, emergency planning and resilience to future flooding.

In vitro biomechanical and hydrodynamic characterisation of decellularised human pulmonary and aortic roots.

BACKGROUND AND PURPOSE OF THE STUDY: The use of decellularised biological heart valves in the replacement of damaged heart valves offers a promising solution to reduce the degradation issues associated with existing cryopreserved allografts. The purpose of this study was to assess the effect of low concentration sodium dodecyl sulphate decellularisation on the in vitro biomechanical and hydrodynamic properties of cryopreserved human aortic and pulmonary roots. METHOD: The biomechanical and hydrodynamic properties of cryopreserved decellularised human aortic and pulmonary roots were fully characterised and compared to cellular human aortic and pulmonary roots in an unpaired study. Following review of these results, a further study was performed to investigate the influence of a specific processing step during the decellularisation protocol ('scraping') in a paired comparison, and to improve the method of the closed valve competency test by incorporating a more physiological boundary condition. RESULTS: The majority of the biomechanical and hydrodynamic characteristics of the decellularised aortic and pulmonary roots were similar compared to their cellular counterparts. However, several differences were noted, particularly in the functional biomechanical parameters of the pulmonary roots. However, in the subsequent paired comparison of pulmonary roots with and without decellularisation, and when a more appropriate physiological test model was used, the functional biomechanical parameters for the decellularised pulmonary roots were similar to the cellular roots. CONCLUSION: Overall, the results demonstrated that the decellularised roots would be a potential choice for clinical application in heart valve replacement.

Association between Berg Balance, Physiological Profile Assessment and Physical Activity, Physical Function and Body Composition: A Cross-sectional Study.

BACKGROUND: Falls are of great concern to older adults and costly to the health system. In addition the relationship between falls risk and falls risk predictor characteristics is complex. OBJECTIVE: This study aimed to explore the relationship between two objective fall-risk measures tools, the Physiological Profile Assessment and the Berg Balance Scale and to determine how an individual's sex, level of physical function, health-related and body composition characteristics impact these objective falls risk measures. DESIGN: A cross-sectional, observational study. PARTICIPANTS: 245 community-dwelling older adults (M age=68.12 years, SD=6.21; 69.8% female). MEASUREMENTS: Participants were assessed for falls-risk (Physiological Profile Assessment and the Berg Balance Scale), physical activity, physical functional and body composition characteristics. Pearson product-moment correlation coefficients were calculated to examine bivariate relationships and hierarchical multiple linear regression modelling was used to estimate the contribution of each predictor in explaining variance in falls-risk. RESULTS: In females, there was a weak association between the two objective falls-risk measures (r =-0.17 p <0.05). The number of falls in the previous 12 months explained 6% of variance in Physiological Profile Assessment scores, with bone density of the lumbar spine contributing a further 1%. In males and females, variance in the Berg Balance Scale showed that age (25%) and physical function (16% for females, 28% for males) contributed significantly to the explaining variance in the falls-risk measure. CONCLUSION: Sex differences are apparent and as such males and females should be assessed (and potentially treated) differently with regards to falls risk. Results indicate that both falls risk assessment tools measure aspects of balance but are not interchangeable. The Berg Balance Scale may be more discriminative in older, less functioning adults and the Physiological Profile Assessment is more useful in assessing falls risk in females.

Comparison of the biomechanical tensile and compressive properties of decellularised and natural porcine meniscus.

Meniscal repair is widely used as a treatment for meniscus injury. However, where meniscal damage has progressed such that repair is not possible, approaches for partial meniscus replacement are now being developed which have the potential to restore the functional role of the meniscus, in stabilising the knee joint, absorbing and distributing stress during loading, and prevent early degenerative joint disease. One attractive potential solution to the current lack of meniscal replacements is the use of decellularised natural biological scaffolds, derived from xenogeneic tissues, which are produced by treating the native tissue to remove the immunogenic cells. The current study investigated the effect of decellularisation on the biomechanical tensile and compressive (indentation and unconfined) properties of the porcine medial meniscus through an experimental-computational approach. The results showed that decellularised medial porcine meniscus maintained the tensile biomechanical properties of the native meniscus, but had lower tensile initial elastic modulus. In compression, decellularised medial porcine meniscus generally showed lower elastic modulus and higher permeability compared to that of the native meniscus. These changes in the biomechanical properties, which ranged from less than 1% to 40%, may be due to the reduction of glycosaminoglycans (GAG) content during the decellularisation process. The predicted biomechanical properties for the decellularised medial porcine meniscus were within the reported range for the human meniscus, making it an appropriate biological scaffold for consideration as a partial meniscus replacement.

Drought as a mental health exposure.

The mental health impact of drought is poorly quantified and no previous research has demonstrated a relationship between distress and explicit environmentally based measures of drought. With continuing climate change, it is important to understand what drought is and how it may affect the mental health. We quantified drought in terms of duration and intensity of relative dryness and identified drought characteristics associated with poor mental health to evaluate any vulnerability in rural and urban communities. Our methods involved analysis of 100-year longitudinal records of monthly rainfall linked to one wave (2007-2008) of the Household, Income and Labour Dynamics in Australia Survey. Cluster analysis was used to characterise different patterns of dryness and linear regression analysis was used to examine associations with participant distress, as well as the moderating role of rural locality. The results showed that, during a seven-year period of major and widespread drought, one pattern of relative dryness (extreme cumulative number of months in drought culminating in a recent period of dryness lasting a year or more) was associated with increased distress for rural but not urban dwellers. The increase in distress was estimated to be 6.22%, based on 95% confidence intervals. Thus, we show that it is possible to quantitatively identify an association between patterns of drought and distress.

Language impairment in cerebellar ataxia.

BACKGROUND: Several studies have suggested that language impairment can be observed in patients with cerebellar pathology. The aim of this study was to investigate language performance in patients with spinocerebellar ataxia type 6 (SCA6). METHODS: We assessed speech and language in 29 SCA6 patients with standardized linquistic tests and correlated this with the severity of ataxia, as quantified by the Scale of Assessment and Rating of Ataxia. RESULTS: Individual patients show mild-to-moderate linguistic impairment. Linguistic abnormalities were most distinct on the writing and comprehension subtests. A strong correlation between severity of ataxia and linguistic performance was consistently found. CONCLUSIONS: This study confirms the occurrence of linguistic impairments in patients with cerebellar degenerative diseases, such as SCA6. The relation between linguistic abnormalities and severity of ataxia provides further evidence for a role of the cerebellum in linguistic processing.

Fast ion surface energy loss and straggling in the surface wake fields.

We have measured the stopping powers and straggling of fast, highly ionized atoms passing through thin bilayer targets made up of metals and insulators. We were surprised to find that the energy losses as well as the straggling depend on the ordering of the target and have small but significantly different values on bilayer reversal. We ascribe this newly found difference in energy loss to the surface energy loss field effect due to the differing surface wake fields as the beam exits the target in the two cases. This finding is validated with experiments using several different projectiles, velocities, and bilayer targets. Both partners of the diatomic molecular ions also display similar results. A comparison of the energy loss results with those of previous theoretical predictions for the surface wake potential for fast ions in solids supports the existence of a self-wake.

A Value Chain Analysis of ghost nets in the Arafura Sea: identifying trans-boundary stakeholders, intervention points and livelihood trade-offs.

Lost or discarded fishing nets are a significant component of marine debris which has trans-boundary impacts in large marine ecosystems. Such 'ghost nets' cause the by-catch of marine fauna and require retrieval from coastlines where they wash up. Identifying the causes of discarded nets and feasible intervention points requires analysis of a complex value chain and the stakeholders within it, yet no studies have attempted this. In this paper we combine Value Chain Analysis, commonly applied to understand value-adding for a commodity, with elements of Life Cycle Assessment and social network analysis to examine the drivers, stakeholders, economic, environmental and social costs and benefits in the life of a trawl net. We use the Arafura Sea as a case study, which is shared by Indonesia, Papua New Guinea and Australia, and is the focus of a Trans-boundary Diagnostic Assessment (TDA) within the Arafura-Timor Seas Ecosystem Action program (ATSEA). We follow a trawl net through four sub-systems: manufacture of webbing in South Korea, fishing and loss by an Indonesian vessel, retrieval as ghost net on the northern Australian coastline by Indigenous rangers, and disposal or re-cycling as 'GhostNet Art' by Indigenous artists. Primary stakeholders along the value chain incur economic and social benefits, and economic and environmental costs. There is an anomaly in the chain between Indonesian fishermen and Indigenous rangers, artists and communities due to the lack of market linkages between these primary stakeholders. The first 'nexus of influence' where reductions in net losses and environmental costs can be achieved is through interactions between GhostNets Australia, the World Wide Fund for Nature and the Australian Government, which can influence Indonesian fishery management institutions and fishing crews. The second nexus is via the international art market which by publicising GhostNet Art can raise awareness amongst fish consumers about the impacts of ghost nets, and hence influence Indonesian fishing companies. GhostNets Australia is a key bridging organisation in the network, linking stakeholders across scales and sub-systems. Feasible preventative interventions are discussed to rectify the anomaly in the value chain. The importance of GhostNets Australia and ATSEA in the evolving adaptive co-management and trans-boundary governance of fisheries is highlighted. However, the prevention of ghost nets will result in trade-offs in benefits for the livelihoods of primary stakeholders. The utility of the method for analysing marine debris in TDAs, and ATSEA in particular, is discussed.

Energetics of paraplegic cycling: adaptations to 12 months of high volume training.

PURPOSE: The efficiency of functional electrical-stimulation (FES) cycling in spinal cord injured and anaesthetised able-bodied cyclists has been found to be about one third of that reported during volitional cycling. The stimulation paradigm itself appears to be the main source of this inefficiency. It is unknown whether a period of high-volume training can induce adaptations that may influence the metabolic and electrical cost of FES cycling. METHOD: 11 individuals with paraplegia completed a 12-month, home-based, progressive FES cycle training programme (up to 5 × 60 min per wk). Stimulation cost, oxygen cost, efficiency and markers of anaerobic metabolism were determined before and after 6 and 12 months of training, during constant work-rate tests. RESULTS: Oxygen cost and efficiency did not significantly change after training. Total stimulation cost and blood lactate values reduced overall, while respiratory exchange ratios remained relatively high. CONCLUSIONS: The high metabolic cost of FES cycling is a result of non-physiological recruitment of predominantly fast muscle fibres. The electrical cost of cycling reduced by 37%, probably due to motor unit hypertrophy, and lactate oxidation capacity improved.

Assessment of the antimicrobial activity of acellular vascular grafts.

Several studies have reported biological vascular grafts to be more resistant to microbial infection than synthetic counterparts in vivo. Indeed, small intestinal submucosa (SIS) materials have previously been reported to be antimicrobial. The aim of this study was to assess the antimicrobial activity and the ability to resist biofilm formation of a novel acellular vascular graft and compare it to commercially available alternatives using a range of organisms: MRSA, MSSA, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa and Candida albicans. This was achieved using a modified disk diffusion assay and extraction of the materials into solution followed by minimum inhibitory concentration assays. To assess resistance to biofilm formation a novel biofilm assay was developed which compared the total colony forming units (CFU) recovered from each material and identification of the percentage of CFU which were loosely attached, residing within the biofilm or attached to the biomaterial. The results indicated a lack of antimicrobial activity for all materials tested, including SIS. The biological materials were more resistant to the formation of a biofilm compared to Dacron.

A theory of rate coding control by intrinsic plasticity effects.

Intrinsic plasticity (IP) is a ubiquitous activity-dependent process regulating neuronal excitability and a cellular correlate of behavioral learning and neuronal homeostasis. Because IP is induced rapidly and maintained long-term, it likely represents a major determinant of adaptive collective neuronal dynamics. However, assessing the exact impact of IP has remained elusive. Indeed, it is extremely difficult disentangling the complex non-linear interaction between IP effects, by which conductance changes alter neuronal activity, and IP rules, whereby activity modifies conductance via signaling pathways. Moreover, the two major IP effects on firing rate, threshold and gain modulation, remain unknown in their very mechanisms. Here, using extensive simulations and sensitivity analysis of Hodgkin-Huxley models, we show that threshold and gain modulation are accounted for by maximal conductance plasticity of conductance that situate in two separate domains of the parameter space corresponding to sub- and supra-threshold conductance (i.e. activating below or above the spike onset threshold potential). Analyzing equivalent integrate-and-fire models, we provide formal expressions of sensitivities relating to conductance parameters, unraveling unprecedented mechanisms governing IP effects. Our results generalize to the IP of other conductance parameters and allow strong inference for calcium-gated conductance, yielding a general picture that accounts for a large repertoire of experimental observations. The expressions we provide can be combined with IP rules in rate or spiking models, offering a general framework to systematically assess the computational consequences of IP of pharmacologically identified conductance with both fine grain description and mathematical tractability. We provide an example of such IP loop model addressing the important issue of the homeostatic regulation of spontaneous discharge. Because we do not formulate any assumptions on modification rules, the present theory is also relevant to other neural processes involving excitability changes, such as neuromodulation, development, aging and neural disorders.

Presence of ATM protein and residual kinase activity correlates with the phenotype in ataxia-telangiectasia: a genotype-phenotype study.

Ataxia-telangiectasia (A-T) is an autosomal recessive neurodegenerative disorder with multisystem involvement and cancer predisposition, caused by mutations in the A-T mutated (ATM) gene. To study genotype-phenotype correlations, we evaluated the clinical and laboratory data of 51 genetically proven A-T patients, and additionally measured ATM protein expression and kinase activity. Patients without ATM kinase activity showed the classical phenotype. The presence of ATM protein, correlated with slightly better immunological function. Residual kinase activity correlated with a milder and essentially different neurological phenotype, absence of telangiectasia, normal endocrine and pulmonary function, normal immunoglobulins, significantly lower X-ray hypersensitivity in lymphocytes, and extended lifespan. In these patients, cancer occurred later in life and generally consisted of solid instead of lymphoid malignancies. The genotypes of severely affected patients generally included truncating mutations resulting in total absence of ATM kinase activity, while patients with milder phenotypes harbored at least one missense or splice site mutation resulting in expression of ATM with some kinase activity. Overall, the phenotypic manifestations in A-T show a continuous spectrum from severe classical childhood-onset A-T to a relatively mild adult-onset disorder, depending on the presence of ATM protein and kinase activity. Each patient is left with a tremendously increased cancer risk.

Neuropathology in classical and variant ataxia-telangiectasia.

Ataxia-telangiectasia (A-T) is classically characterized by progressive neurodegeneration, oculocutaneous telangiectasia, immunodeficiency and elevated α-fetoprotein levels. Some patients, classified as variant A-T, exhibit a milder clinical course. In the latter patients extrapyramidal symptoms, instead of cerebellar ataxia, tend to be the dominating feature and other classical disease hallmarks, like telangiectasia, appear later or even may be absent. Some patients with variant disease have clinically pronounced anterior horn cell degeneration. Neuropathological studies of genetically proven A-T patients are lacking. The aims of our study were to describe the neuropathology of three A-T patients; in two of them the diagnosis was genetically confirmed. The neuropathological findings were compared with those of all known published autopsy findings in A-T patients up to now. Two classical A-T patients aged 19 and 22 and a 33-year-old patient with variant disease were autopsied. In line with previous reports, our patients had severe cerebellar atrophy, less pronounced degeneration of the dentate nucleus and inferior olive, degeneration of the posterior columns and neurogenic muscular atrophy. In addition, all three had anterior horn cell degeneration, which was most prominent at the lumbar level. Compared to the literature, the degenerative changes in the brain stem of the variant A-T patient were somewhat less than anticipated for his age. Degenerative changes in the cerebellum and spinal cord were comparable with those in the literature. Progeric changes were lacking. In conclusion, compared to classical A-T, the variant A-T patient showed essentially the same, only slightly milder neuropathological abnormalities, except for anterior horn degeneration.

Imminent brain death: point of departure for potential heart-beating organ donor recognition.

PURPOSE: There is, in European countries that conduct medical chart review of intensive care unit (ICU) deaths, no consensus on uniform criteria for defining a potential organ donor. Although the term is increasingly being used in recent literature, it is seldom defined in detail. We searched for criteria for determination of imminent brain death, which can be seen as a precursor for organ donation. METHODS: We organized meetings with representatives from the field of clinical neurology, neurotraumatology, intensive care medicine, transplantation medicine, clinical intensive care ethics, and organ procurement management. During these meetings, all possible criteria were discussed to identify a patient with a reasonable probability to become brain dead (imminent brain death). We focused on the practical usefulness of two validated coma scales (Glasgow Coma Scale and the FOUR Score), brain stem reflexes and respiration to define imminent brain death. Further we discussed criteria to determine irreversibility and futility in acute neurological conditions. RESULTS: A patient who fulfills the definition of imminent brain death is a mechanically ventilated deeply comatose patient, admitted to an ICU, with irreversible catastrophic brain damage of known origin. A condition of imminent brain death requires either a Glasgow Coma Score of 3 and the progressive absence of at least three out of six brain stem reflexes or a FOUR score of E(0)M(0)B(0)R(0). CONCLUSION: The definition of imminent brain death can be used as a point of departure for potential heart-beating organ donor recognition on the intensive care unit or retrospective medical chart analysis.

Design and validation of a conformation sensitive capillary electrophoresis-based mutation scanning system and automated data analysis of the more than 15 kbp-spanning coding sequence of the SACS gene.

In this study, we developed and analytically validated a fully automated, robust confirmation sensitive capillary electrophoresis (CSCE) method to perform mutation scanning of the large SACS gene. This method facilitates a rapid and cost-effective molecular diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay. Critical issues addressed during the development of the CSCE system included the position of a DNA variant relative to the primers and the CG-content of the amplicons. The validation was performed in two phases; a retrospective analysis of 32 samples containing 41 different known DNA variants and a prospective analysis of 20 samples of patients clinically suspected of having autosomal recessive spastic ataxia of Charlevoix-Saguenay. These 20 samples appeared to contain 73 DNA variants. In total, in 32 out of the 45 amplicons, a DNA variant was present, which allowed verification of the detection capacity during the validation process. After optimization of the original design, the overall analytical sensitivity of CSCE for the SACS gene was 100%, and the analytical specificity of CSCE was 99.8%. In conclusion, CSCE is a robust technique with a high analytical sensitivity and specificity, and it can readily be used for mutation scanning of the large SACS gene. Furthermore this technique is less time-consuming and less expensive, as compared with standard automated sequencing.

Determination and possible application of the aerobic gas exchange threshold in aerobically untrained paraplegic subjects based on stimulated cycle ergometry.

PURPOSE: To accurately characterise cardiopulmonary baseline performance in aerobically untrained paraplegic subjects by means of an incremental exercise test (IET) and to derive possible training recommendations based on these measurements. METHODS: Twelve motor complete paraplegic subjects with no previous experience in stimulated leg-cycling participated in the study. Exercise testing was performed on a recumbent FES-tricycle by means of a work rate and cadence controlled IET until maximal work rate was reached. Heart rate (HR) and respiratory parameters were recorded continuously. RESULTS: Peak oxygen uptake was 671 +/- 192 mL min(-1) (mean + standard deviation), peak HR 90 +/- 12 beats min(-1), net peak power 8.4 +/- 3.3 W and peak minute ventilation 23.6 +/- 7.5 L min(-1). Aerobic gas exchange threshold (GET) was found to be 51% +/- 10% of peak oxygen uptake and corresponded to 41% +/- 13% of peak power. CONCLUSIONS: A cadence and work rate controlled exercise test allows the determination of cardiopulmonary parameters during stimulated cycle ergometry even in aerobically untrained paraplegic subjects. The precise determination of GET allows an appropriate exercise intensity to be prescribed and thus provides a suitable method for exercise intensity calculation in the spinal cord injured population in the future.

Dose-finding study of weekly docetaxel, epirubicin and capecitabine, as first-line treatment in advanced breast cancer.

BACKGROUND: Combinations of anthracycline, taxane and fluoropyrimidine are highly active in advanced breast cancer (ABC). In a phase II study of epirubicin 50 mg/m(2), docetaxel 75 mg/m(2), and infusional 5-FU 200 mg/m(2)/day, we found dose-limiting neutropenia and frequent central venous catheter complications. An alternative approach has been tested using weekly fractionation of docetaxel, and oral capecitabine. METHODS: Initially, six women with ABC were treated with epirubicin 60 mg/m(2) day 1, docetaxel 25 mg/m(2) days 1,8,15, and capecitabine 1,000 mg/m(2) twice daily days 1-14, every 21 days. Six further patients received the above with capecitabine escalated to 1,500 mg/m(2) RESULTS: Four DLTs occurred in six patients at the second dose level (febrile neutropenia in 2). There were frequent dose delays/reductions, and fatigue, nausea/vomiting, and diarrhoea were common. Overall, six of ten assessable patients achieved a partial response. CONCLUSIONS: An active regimen, but significant haematological toxicity precluded dose further escalation.

Differentiation of hereditary spastic paraparesis from primary lateral sclerosis in sporadic adult-onset upper motor neuron syndromes.

OBJECTIVE: To study whether clinical characteristics can differentiate sporadic presentations of hereditary spastic paraparesis (HSP) from primary lateral sclerosis (PLS). Differentiation between these diseases is important for genetic counseling and prognostication. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: One hundred four Dutch patients with an adult-onset, sporadic upper motor neuron syndrome of at least 3 years' duration. Hereditary spastic paraparesis was genetically confirmed in 14 patients (7 with SPG4 and 7 with SPG7 mutations). RESULTS: All 14 patients with the SPG4 or SPG7 mutation had symptom onset in the legs, and 1 of the patients with the SPG7 mutation also developed symptoms in the arms. Of the other 90 patients, 78 (87%) had symptom onset in the legs. Thirty-six patients developed a PLS phenotype (bulbar region involvement), 15 had a phenotype that was difficult to classify as similar to HSP or PLS (involvement of legs and arms only), and 39 continued to have a phenotype similar to typical HSP (involvement of the legs only). Median age at onset was lower in patients with the SPG4 or SPG7 mutation (39 [range, 29-69] years), but there was considerable overlap with patients with the PLS phenotype (52 [range, 32-76] years). No differences were found in the features used by previous studies to distinguish HSP from PLS, including evidence of mild dorsal column impairment (decreased vibratory sense or abnormal leg somatosensory evoked potentials), symptoms of urinary urgency, or mild electromyographic abnormalities. CONCLUSIONS: In most patients with a sporadic adult-onset upper motor neuron syndrome, differentiation of sporadic presentations of HSP from PLS based on clinical characteristics is unreliable and therefore depends on results of genetic testing.

Short-term symptom and quality-of-life comparison between laparoscopic Nissen and Toupet fundoplications.

Laparoscopic antireflux surgery is an established method of treatment of gastroesophageal reflux disease (GERD). This study evaluates the efficacy of Nissen versus Toupet fundoplication in alleviating the symptoms of GERD and compares the two techniques for the development of post-fundoplication symptoms and quality of life (QOL) at 12 months post-surgery. In this prospective consecutive cohort study, 94 patients presenting for laparoscopic antireflux surgery underwent either laparoscopic Nissen fundoplication (LN) (n = 51) from February 2002 to February 2004 or a laparoscopic Toupet fundoplication (LT) (n = 43) from March 2004 to March 2006, performed by a single surgeon (G. S. S.). Symptom assessment, a QOL scoring instrument, and dysphagia questionnaires were applied pre- and postoperatively. At 12 months post-surgery, patient satisfaction levels in both groups were high and similar (LT: 98%, LN: 90%; P = 0.21). The proportion of patients reporting improvement in their reflux symptoms was similar in both groups (LT: 95%, LN: 92%; P = 0.68), as were post-fundoplication symptoms (LT: 30%, LN: 37%; P = 0.52). Six patients in the Nissen group required dilatation for dysphagia compared with one in the Toupet group (LT: 2%, LN: 12%; P = 0.12). One patient in the Nissen group required conversion to Toupet for persistent dysphagia (P = 0.54). In this series, overall symptom improvement, QOL, and patient satisfaction were equivalent 12 months following laparoscopic Nissen or Toupet fundoplication. There was no difference in post-fundoplication symptoms between the two groups, although there was a trend toward a higher dilatation requirement and reoperation after Nissen fundoplication.