Northland District Health Board

OBJECTIVES: This guideline provides recommendations for the clinical management of schizophrenia and related disorders for health professionals working in Australia and New Zealand. It aims to encourage all clinicians to adopt best practice principles. The recommendations represent the consensus of a group of Australian and New Zealand experts in the management of schizophrenia and related disorders. This guideline includes the management of ultra-high risk syndromes, first-episode psychoses and prolonged psychoses, including psychoses associated with substance use. It takes a holistic approach, addressing all aspects of the care of people with schizophrenia and related disorders, not only correct diagnosis and symptom relief but also optimal recovery of social function. METHODS: The writing group planned the scope and individual members drafted sections according to their area of interest and expertise, with reference to existing systematic reviews and informal literature reviews undertaken for this guideline. In addition, experts in specific areas contributed to the relevant sections. All members of the writing group reviewed the entire document. The writing group also considered relevant international clinical practice guidelines. Evidence-based recommendations were formulated when the writing group judged that there was sufficient evidence on a topic. Where evidence was weak or lacking, consensus-based recommendations were formulated. Consensus-based recommendations are based on the consensus of a group of experts in the field and are informed by their agreement as a group, according to their collective clinical and research knowledge and experience. Key considerations were selected and reviewed by the writing group. To encourage wide community participation, the Royal Australian and New Zealand College of Psychiatrists invited review by its committees and members, an expert advisory committee and key stakeholders including professional bodies and special interest groups. RESULTS: The clinical practice guideline for the management of schizophrenia and related disorders reflects an increasing emphasis on early intervention, physical health, psychosocial treatments, cultural considerations and improving vocational outcomes. The guideline uses a clinical staging model as a framework for recommendations regarding assessment, treatment and ongoing care. This guideline also refers its readers to selected published guidelines or statements directly relevant to Australian and New Zealand practice. CONCLUSIONS: This clinical practice guideline for the management of schizophrenia and related disorders aims to improve care for people with these disorders living in Australia and New Zealand. It advocates a respectful, collaborative approach; optimal evidence-based treatment; and consideration of the specific needs of those in adverse circumstances or facing additional challenges.

Germline CDH1 mutations confer a high lifetime risk of developing diffuse gastric (DGC) and lobular breast cancer (LBC). A multidisciplinary workshop was organised to discuss genetic testing, surgery, surveillance strategies, pathology reporting and the patient's perspective on multiple aspects, including diet post gastrectomy. The updated guidelines include revised CDH1 testing criteria (taking into account first-degree and second-degree relatives): (1) families with two or more patients with gastric cancer at any age, one confirmed DGC; (2) individuals with DGC before the age of 40 and (3) families with diagnoses of both DGC and LBC (one diagnosis before the age of 50). Additionally, CDH1 testing could be considered in patients with bilateral or familial LBC before the age of 50, patients with DGC and cleft lip/palate, and those with precursor lesions for signet ring cell carcinoma. Given the high mortality associated with invasive disease, prophylactic total gastrectomy at a centre of expertise is advised for individuals with pathogenic CDH1 mutations. Breast cancer surveillance with annual breast MRI starting at age 30 for women with a CDH1 mutation is recommended. Standardised endoscopic surveillance in experienced centres is recommended for those opting not to have gastrectomy at the current time, those with CDH1 variants of uncertain significance and those that fulfil hereditary DGC criteria without germline CDH1 mutations. Expert histopathological confirmation of (early) signet ring cell carcinoma is recommended. The impact of gastrectomy and mastectomy should not be underestimated; these can have severe consequences on a psychological, physiological and metabolic level. Nutritional problems should be carefully monitored.

Importance: The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer. Observations: Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts. Conclusions and Relevance: The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

OBJECTIVE: Implementation of machine learning (ML) may be limited by patients' right to "meaningful information about the logic involved" when ML influences healthcare decisions. Given the complexity of healthcare decisions, it is likely that ML outputs will need to be understood and trusted by physicians, and then explained to patients. We therefore investigated the association between physician understanding of ML outputs, their ability to explain these to patients, and their willingness to trust the ML outputs, using various ML explainability methods. MATERIALS AND METHODS: We designed a survey for physicians with a diagnostic dilemma that could be resolved by an ML risk calculator. Physicians were asked to rate their understanding, explainability, and trust in response to 3 different ML outputs. One ML output had no explanation of its logic (the control) and 2 ML outputs used different model-agnostic explainability methods. The relationships among understanding, explainability, and trust were assessed using Cochran-Mantel-Haenszel tests of association. RESULTS: The survey was sent to 1315 physicians, and 170 (13%) provided completed surveys. There were significant associations between physician understanding and explainability (P < .001), between physician understanding and trust (P < .001), and between explainability and trust (P < .001). ML outputs that used model-agnostic explainability methods were preferred by 88% of physicians when compared with the control condition; however, no particular ML explainability method had a greater influence on intended physician behavior. CONCLUSIONS: Physician understanding, explainability, and trust in ML risk calculators are related. Physicians preferred ML outputs accompanied by model-agnostic explanations but the explainability method did not alter intended physician behavior.

BACKGROUND: Stiffness complicating TKA is a complex and multifactorial problem. We suspected internally rotated components compromised motion because of pain, patellar maltracking, a tight medial flexion gap, and limited femoral rollback on a conforming lateral tibial condyle. QUESTIONS/PURPOSES: We sought to determine: (1) the incidence of internal rotation of the femoral and tibial components in stiff TKAs; (2) if revision surgery that included correction of rotational positioning improved pain, ROM, and patellar tracking; and (3) if revision altered nonrotational radiographic parameters. METHODS: From a cohort of 52 patients with TKAs revised for stiffness, we performed CT scans of 34 before and 18 after revision to quantify rotational positioning of the femoral and tibial components using a previously validated scanning protocol. RESULTS: All 34 patients with TKAs had internal rotation of the summed values for tibial and femoral components (mean, 14.8°; range, 2.7°-33.7°) before revision for stiffness. The incidence of internal rotation was 24 of 34 femoral (mean, 3.1°; internal) and 33 of 34 tibial components (mean, 13.7° internal). Revision arthroplasty improved Knee Society function, knee, and pain scores. Mean extension improved from a contracture of 10.1° to 0.8° and flexion from 71.5° to 100°. Postrevision CT scans confirmed correction of component rotation. Nonrotational parameters were unchanged. CONCLUSIONS: We recommend CT scanning of patients with stiff TKAs before surgical intervention to identify the presence of internally rotated components. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

BACKGROUND: Alveolar bone changes following tooth extraction can compromise prosthodontic rehabilitation. Alveolar ridge preservation (ARP) has been proposed to limit these changes and improve prosthodontic and aesthetic outcomes when implants are used. This is an update of the Cochrane Review first published in 2015. OBJECTIVES: To assess the clinical effects of various materials and techniques for ARP after tooth extraction compared with extraction alone or other methods of ARP, or both, in patients requiring dental implant placement following healing of extraction sockets. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 19 March 2021), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2021, Issue 2), MEDLINE Ovid (1946 to 19 March 2021), Embase Ovid (1980 to 19 March 2021), Latin American and Caribbean Health Science Information database (1982 to 19 March 2021), Web of Science Conference Proceedings (1990 to 19 March 2021), Scopus (1966 to 19 March 2021), ProQuest Dissertations and Theses (1861 to 19 March 2021), and OpenGrey (to 19 March 2021). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. A number of journals were also handsearched. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) on the use of ARP techniques with at least six months of follow-up. Outcome measures were: changes in the bucco-lingual/palatal width of alveolar ridge, changes in the vertical height of the alveolar ridge, complications, the need for additional augmentation prior to implant placement, aesthetic outcomes, implant failure rates, peri-implant marginal bone level changes, changes in probing depths and clinical attachment levels at teeth adjacent to the extraction site, and complications of future prosthodontic rehabilitation. DATA COLLECTION AND ANALYSIS: We selected trials, extracted data, and assessed risk of bias in duplicate. Corresponding authors were contacted to obtain missing information. We estimated mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes, with 95% confidence intervals (95% CI). We constructed 'Summary of findings' tables to present the main findings and assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 16 RCTs conducted worldwide involving a total of 524 extraction sites in 426 adult participants. We assessed four trials as at overall high risk of bias and the remaining trials at unclear risk of bias. Nine new trials were included in this update with six new trials in the category of comparing ARP to extraction alone and three new trials in the category of comparing different grafting materials. ARP versus extraction: from the seven trials comparing xenografts with extraction alone, there is very low-certainty evidence of a reduction in loss of alveolar ridge width (MD -1.18 mm, 95% CI -1.82 to -0.54; P = 0.0003; 6 studies, 184 participants, 201 extraction sites), and height (MD -1.35 mm, 95% CI -2.00 to -0.70; P < 0.0001; 6 studies, 184 participants, 201 extraction sites) in favour of xenografts, but we found no evidence of a significant difference for the need for additional augmentation (RR 0.68, 95% CI 0.29 to 1.62; P = 0.39; 4 studies, 154 participants, 156 extraction sites; very low-certainty evidence) or in implant failure rate (RR 1.00, 95% CI 0.07 to 14.90; 2 studies, 70 participants/extraction sites; very low-certainty evidence). From the one trial comparing alloplasts versus extraction, there is very low-certainty evidence of a reduction in loss of alveolar ridge height (MD -3.73 mm; 95% CI -4.05 to -3.41; 1 study, 15 participants, 60 extraction sites) in favour of alloplasts. This single trial did not report any other outcomes. Different grafting materials for ARP: three trials (87 participants/extraction sites) compared allograft versus xenograft, two trials (37 participants, 55 extraction sites) compared alloplast versus xenograft, one trial (20 participants/extraction sites) compared alloplast with and without membrane, one trial (18 participants, 36 extraction sites) compared allograft with and without synthetic cell-binding peptide P-15, and one trial (30 participants/extraction sites) compared alloplast with different particle sizes. The evidence was of very low certainty for most comparisons and insufficient to determine whether there are clinically significant differences between different ARP techniques based on changes in alveolar ridge width and height, the need for additional augmentation prior to implant placement, or implant failure. We found no trials which evaluated parameters relating to clinical attachment levels, specific aesthetic or prosthodontic outcomes for any of the comparisons. No serious adverse events were reported with most trials indicating that the procedure was uneventful. Among the complications reported were delayed healing with partial exposure of the buccal plate at suture removal, postoperative pain and swelling, moderate glazing, redness and oedema, membrane exposure and partial loss of grafting material, and fibrous adhesions at the cervical part of previously preserved sockets, for the comparisons xenografts versus extraction, allografts versus xenografts, alloplasts versus xenografts, and alloplasts with and without membrane. AUTHORS' CONCLUSIONS: ARP techniques may minimise the overall changes in residual ridge height and width six months after extraction but the evidence is very uncertain. There is lack of evidence of any differences in the need for additional augmentation at the time of implant placement, implant failure, aesthetic outcomes, or any other clinical parameters due to lack of information or long-term data. There is no evidence of any clinically significant difference between different grafting materials and barriers used for ARP. Further long-term RCTs that follow CONSORT guidelines (www.consort-statement.org) are necessary.

BackgroundGuidelines preferentially recommend noncalcium phosphate binders in adults with chronic kidney disease (CKD). We compare and rank phosphate-binder strategies for CKD.Study DesignNetwork meta-analysis.Setting & PopulationAdults with CKD.Selection Criteria for StudiesRandomized trials with allocation to phosphate binders.InterventionsSevelamer, lanthanum, iron, calcium, colestilan, bixalomer, nicotinic acid, and magnesium.OutcomesThe primary outcome was all-cause mortality. Additional outcomes were cardiovascular mortality, myocardial infarction, stroke, adverse events, serum phosphorus and calcium levels, and coronary artery calcification.Results77 trials (12,562 participants) were included. Most (62 trials in 11,009 patients) studies were performed in a dialysis population. Trials were generally of short duration (median, 6 months) and had high risks of bias. All-cause mortality was ascertained in 20 studies during 86,744 patient-months of follow-up. There was no evidence that any drug class lowered mortality or cardiovascular events when compared to placebo. Compared to calcium, sevelamer reduced all-cause mortality (OR, 0.39; 95% CI, 0.21-0.74), whereas treatment effects of lanthanum, iron, and colestilan were not significant (ORs of 0.78 [95% CI, 0.16-3.72], 0.37 [95% CI, 0.09-1.60], and 0.55 [95% CI, 0.07-4.43], respectively). Lanthanum caused nausea, whereas sevelamer posed the highest risk for constipation and iron caused diarrhea. All phosphate binders lowered serum phosphorus levels to a greater extent than placebo, with iron ranked as the best treatment. Sevelamer and lanthanum posed substantially lower risks for hypercalcemia than calcium.LimitationsLimited testing of consistency; short follow-up.ConclusionsThere is currently no evidence that phosphate-binder treatment reduces mortality compared to placebo in adults with CKD. It is not clear whether the higher mortality with calcium versus sevelamer reflects whether there is net harm associated with calcium, net benefit with sevelamer, both, or neither. Iron-based binders show evidence of greater phosphate lowering that warrants further examination in randomized trials. Guidelines preferentially recommend noncalcium phosphate binders in adults with chronic kidney disease (CKD). We compare and rank phosphate-binder strategies for CKD. Network meta-analysis. Adults with CKD. Randomized trials with allocation to phosphate binders. Sevelamer, lanthanum, iron, calcium, colestilan, bixalomer, nicotinic acid, and magnesium. The primary outcome was all-cause mortality. Additional outcomes were cardiovascular mortality, myocardial infarction, stroke, adverse events, serum phosphorus and calcium levels, and coronary artery calcification. 77 trials (12,562 participants) were included. Most (62 trials in 11,009 patients) studies were performed in a dialysis population. Trials were generally of short duration (median, 6 months) and had high risks of bias. All-cause mortality was ascertained in 20 studies during 86,744 patient-months of follow-up. There was no evidence that any drug class lowered mortality or cardiovascular events when compared to placebo. Compared to calcium, sevelamer reduced all-cause mortality (OR, 0.39; 95% CI, 0.21-0.74), whereas treatment effects of lanthanum, iron, and colestilan were not significant (ORs of 0.78 [95% CI, 0.16-3.72], 0.37 [95% CI, 0.09-1.60], and 0.55 [95% CI, 0.07-4.43], respectively). Lanthanum caused nausea, whereas sevelamer posed the highest risk for constipation and iron caused diarrhea. All phosphate binders lowered serum phosphorus levels to a greater extent than placebo, with iron ranked as the best treatment. Sevelamer and lanthanum posed substantially lower risks for hypercalcemia than calcium. Limited testing of consistency; short follow-up. There is currently no evidence that phosphate-binder treatment reduces mortality compared to placebo in adults with CKD. It is not clear whether the higher mortality with calcium versus sevelamer reflects whether there is net harm associated with calcium, net benefit with sevelamer, both, or neither. Iron-based binders show evidence of greater phosphate lowering that warrants further examination in randomized trials.

We report a broader than previously appreciated clinical spectrum for hereditary sensory and autonomic neuropathy type 1E (HSAN1E) and a potential pathogenic mechanism for DNA methyltransferase (DNMT1) mutations. The clinical presentations and genetic characteristics of nine newly identified HSAN1E kinships (45 affected subjects) were investigated. Five novel mutations of DNMT1 were discovered; p.C353F, p.T481P, p.P491L, p.Y524D and p.I531N, all within the target-sequence domain, and two mutations (p.T481P, p.P491L) arising de novo. Recently, HSAN1E has been suggested as an allelic disorder of autosomal dominant cerebellar ataxia, deafness and narcolepsy. Our results indicate that all the mutations causal for HSAN1E are located in the middle part or N-terminus end of the TS domain, whereas all the mutations causal for autosomal dominant cerebellar ataxia, deafness and narcolepsy are located in the C-terminus end of the TS domain. The impact of the seven causal mutations in this cohort was studied by cellular localization experiments. The binding efficiency of the mutant DNMT proteins at the replication foci and heterochromatin were evaluated. Phenotypic characterizations included electromyography, brain magnetic resonance and nuclear imaging, electroencephalography, sural nerve biopsies, sleep evaluation and neuropsychometric testing. The average survival of HSAN1E was 53.6 years. [standard deviation = 7.7, range 43-75 years], and mean onset age was 37.7 years. (standard deviation = 8.6, range 18-51 years). Expanded phenotypes include myoclonic seizures, auditory or visual hallucinations, and renal failure. Hypersomnia, rapid eye movement sleep disorder and/or narcolepsy were identified in 11 subjects. Global brain atrophy was found in 12 of 14 who had brain MRI. EEGs showed low frequency (delta waves) frontal-predominant abnormality in five of six patients. Marked variability in cognitive deficits was observed, but the majority of patients (89%) developed significant cognitive deficit by the age of 45 years. Cognitive function decline often started with personality changes and psychiatric manifestations. A triad of hearing loss, sensory neuropathy and cognitive decline remains as the stereotypic presentation of HSAN1E. Moreover, we show that mutant DNMT1 proteins translocate to the cytoplasm and are prone to form aggresomes while losing their binding ability to heterochromatin during the G2 cell cycle. Our results suggest mutations in DNMT1 result in imbalanced protein homeostasis through aggresome-induced autophagy. This mechanism may explain why mutations in the sole DNA maintenance methyltransferase lead to selective central and peripheral neurodegeneration.

Abstract A reappraisal of the conservation status of the indigenous New Zealand vascular plant flora is presented using the 2008 version of the threat classification system developed for the New Zealand Department of Conservation. The list comprises 897 taxa (38% of New Zealand's total indigenous vascular flora) in the following categories: Extinct—6 taxa, Threatened—180 taxa (comprising 91 Nationally Critical taxa, 45 Nationally Endangered, and 44 Nationally Vulnerable), At Risk—651 taxa (comprising 83 Declining, 6 Recovering, 20 Relict, and 542 Naturally Uncommon taxa), 25 taxa listed as either Vagrant (12) or Coloniser (13), and 35 as Data Deficient. A further 171 plants are listed as taxonom ically indeterminate, being those which might warrant further conservation attention once their taxonomic status is clarified. Forty‐four recognised taxa and 26 plants rated as taxonomically indeterminate, and previously considered to be threatened and/or uncommon, are removed from this updated listing. A brief analysis of the patterns of rarity exhibited by the listed taxa is presented. Overall, the conservation status of the New Zealand indigenous vascular plant flora is worsening, with 7.6% of this flora now regarded as threatened with extinction. A concordance of plants names from the 2004 listing is provided.

Unmanned aerial systems (UAS), commonly referred to as drones, are finding applications in several ecological research areas since remotely piloted aircraft (RPA) technology has ceased to be a military prerogative. Fixed-wing RPA have been tested for line transect aerial surveys of geographically dispersed marine mammal species. Despite many advantages, their systematic use is far from a reality. Low altitude, long endurance systems are still highly priced. Regulatory bodies also impose limitations while struggling to cope with UAS rapid technological evolution. In contrast, small vertical take-off and landing (VTOL) UAS have become increasingly affordable but lack the flight endurance required for long-range aerial surveys. Although this issue and civil aviation regulations prevent the use of VTOL UAS for marine mammal abundance estimation on a large scale, recent studies have highlighted other potential applications. The present note represents a general overview on the use of UAS as a survey tool for marine mammal studies. The literature pertaining to UAS marine mammal research applications is considered with special concern for advantages and limitations of the survey design. The use of lightweight VTOL UAS to collect marine mammal behavioral data is also discussed.

The Anaesthetic Trainee Theatre Educational Environment Measure (ATEEM) was developed to measure the educational environment for trainee anaesthetists in the theatre setting using similar methodology to that of other existing tools. The ATEEM was administered to 271 anaesthetic trainees three months into their post of whom 218 (80%) responded. The ATEEM showed that trainees' perceptions of their educational environments do vary and that this inventory is capable of identifying problem areas that can be remediated by training managers.

A procedure has been devised for treatment of the inability to extend the elbow due to either a fixed contracture of the flexor muscles or increased involuntary flexor-muscle tone and spasticity. The operation consists of lengthening all of the primary elbow-flexor muscles. It has been used successfully in thirty-two elbows of twenty-six children with cerebral palsy who were followed for an average of four years (range, two through six years). The average gain in extension was 40 degrees, and there was no loss of the patient's ability to flex the elbow or supinate the forearm. No vascular or neural complications were encountered. Independence in feeding was achieved in four patients. Seven patient acquired the ability to engage in sports and six, who previously had been unable to walk independently due to inability to handle crutches, could do so following this procedure.

Abstract We compared the proportion of common wasps ( Vespula vulgaris ) in samples sent to us by members of the public with the proportion in samples sent by beekeepers from their apiaries. Common wasps robbed beehives less frequently than German wasps ( V. germanica ) relative to their population levels in the environment. A questionnaire was sent to 600 beekeepers throughout New Zealand asking for information on the impact of wasps on their operations in the 1985/86 and 1986/87 seasons. The majority (83.8%) of the 278 respondents considered wasps to be a nuisance. Beekeepers found more wasps nests in areas with (referred to as “vulgaris” areas) than without the common wasp (“non‐vulgaris” areas), even though they spent no more time in wasp control. Similar numbers of overwintering nests were found in vulgaris and nonvulgaris zones. Overwintering nests were more common, and wasps caused more problems during spring buildup in the North Island than the South Island. Wasps totally destroyed or seriously affected 8.13% of hives in 1985/86 and 9.35% in 1986/87. South Island beekeepers in honeydew beech forests where common wasps were present faced greater hive damage levels than beekeepers elsewhere in the country. However, the increase in damage between the two seasons was much lower than the increase in the wasp population over the same time. Further, the number of hives totally destroyed by wasps in the common wasp infested regions of the South Island changed little between seasons. The increased damage levels resulted mostly from an increase in seriously affected hives. It is concluded that high wasp abundance was probably the reason for the high hive damage levels in the honeydew forests in 1986/87. This was offset by the low rate of robbing and lack of overwintering nests of the common wasp, which poses less of a threat than the German wasp to the New Zealand beekeeping industry.

Macrophages appear to have a fundamental role in the pathogenesis of osteosarcoma. These highly diverse plastic cells are subdivided into classical or inflammatory macrophages known as M1 and alternative macrophages, which decrease inflammation and are reparative, called M2. Although primary and metastatic osteosarcomas are infiltrated with M2 macrophages, targeting the M1 macrophages with the immune adjuvant muramyl tripeptide phosphatidyl ethanolamine (MTP-PE) has been the greatest recent therapeutic advance in osteosarcoma. This discrepancy between the presence of M2 and activation of M1 macrophages is intriguing and is likely explained either by the plasticity of M1 and M2 macrophages or nonclassical patrolling monocytes (PMos). To date, MTP-PE has been approved in combination with chemotherapy for nonmetastatic osteosarcoma, but its use in metastatic tumors has not been investigated. In this review, we focus on macrophages, monocytes, and osteoclasts, their role in osteosarcoma, and the potential for targeting these cells in this disease.

What's known on the subject? and What does the study add? Benign prostatic hyperplasia ( BPH ) is the most frequent benign neoplasm in ageing men. Histological studies have shown that intraprostatic inflammatory infiltration is seen in 43–98% of BPH tissues. Preclinical investigations have shown inhibition of growth in the BPH cell line in vitro after treatment with NSAIDs . This review provides evidence that NSAIDs result in improved symptoms and urinary flow associated with BPH . Further research and larger clinical trials are needed to assess the safety and long‐term impact of NSAID use in men with BPH . From the clinical viewpoint, the development of substances that can inhibit inflammatory changes in the hyperplastic prostate may provide new treatment strategies. Objective To assess the effects of non‐steroidal anti‐inflammatory drugs ( NSAIDs ) in men with benign prostatic hyperplasia ( BPH ) using systematic review and meta‐analysis of clinical trials. Subjects Men treated with NSAIDs in comparison with placebo or other BPH medications. Methods All aspects of the P referred R eporting for S ystematic R eviews and M eta‐ A nalyses ( PRISMA ) statement were followed. Trials were eligible for inclusion provided they (i) randomized men with BPH to receive NSAIDs in comparison with placebo or other BPH medications, and (ii) included clinical outcomes such as urological symptom scales, symptoms or urodynamic measurements. Data analysis was performed using R eview M anager Version 5.0 software. Study weight was calculated by the inverse variances of the study effect estimates. Results In all, 183 men from three randomized, placebo‐controlled trials (lasting 4–24 weeks) were assessed. NSAIDs improved urinary symptom scores and flow measures. The weighted mean difference for the International Prostate Symptom Score ( IPSS ) was −2.89 IPSS points (95% CI −3.84 to −1.95, P &lt; 0.001, n = 3 studies). The weighted mean difference for peak urine flow was 0.89 mL/s (95% CI 0.21–1.58, P = 0.01, n = 3 studies) and for reported adverse effects was 1.51 (95% CI 0.66–3.43, P = 0.32, n = 3 studies,). All patients assigned to NSAIDs continued the treatment. There were no serious adverse effects and there were no withdrawals or losses to follow‐up. Conclusion The evidence suggests that NSAIDs improve urinary symptoms and flow measures. Their long‐term effectiveness, safety and ability to prevent BPH complications are not known.

Objectives The purpose of this study was to determine the long-term efficacy, safety and rate of recurrence for varicose veins associated with great saphenous vein (GSV) reflux treated with ultrasound-guided foam sclerotherapy (UGFS). Methods A five-year prospective study was performed, recording the effect on the GSV and saphenofemoral junction (SFJ) diameters, and reflux in the superficial venous system over time. UGFS was the sole treatment modality used in all cases, and repeat UGFS was performed where indicated following serial annual ultrasound. Results No serious adverse outcomes were observed – specifically no thromboembolism, arterial injection, anaphylaxis or nerve damage. There was a 4% clinical recurrence rate after five years, with 100% patient acceptance of success. Serial annual duplex ultrasound demonstrated a significant reduction in GSV and SFJ diameters, maintained over time. There was ultrasound recurrence in 27% at 12 months, and in 64% at five years, including any incompetent trunkal or tributary reflux even 1 mm in diameter being recorded. Thirty percent had pure ultrasound recurrence, 17% new vessel reflux and 17% combined new and recurrent vessels on ultrasound. Of all, 16.5% required repeat UGFS treatment between 12 and 24 months, but less than 10% in subsequent years. The safety and clinical efficacy of UGFS for all clinical, aetiological, anatomical and pathological elements classes of GSV reflux was excellent. Conclusion The popularity of this outpatient technique with patients reflects ease of treatment, lower cost, lack of downtime and elimination of venous signs and symptoms. Patients accept that UGFS can be repeated readily if required for recurrence in this common chronic condition. The subclinical ultrasound evidence of recanalization or new vein incompetence needs to be considered in this light.

Apolipoprotein-E (apo-E) genotyping has been investigated as an indicator of susceptibility to heavy metal (i.e., lead) neurotoxicity. Moreover, the apo-E epsilon (epsilon)4 allele is a major risk factor for neurodegenerative conditions, including Alzheimer's disease (AD). A theoretical biochemical basis for this risk factor is discussed herein, supported by data from 400 patients with presumptive mercury-related neuro-psychiatric symptoms and in whom apo-E determinations were made. A statistically relevant shift toward the at-risk apo-E epsilon4 groups was found in the patients p<0.001). The patients possessed a mean of 13.7 dental amalgam fillings and 31.5 amalgam surfaces. This far exceeds the number capable of producing the maximum identified tolerable daily intake of mercury from amalgam. The clinical diagnosis and proof of chronic low-level mercury toxicity has been difficult due to the non-specific nature of the symptoms and signs. Dental amalgam is the greatest source of mercury in the general population and brain, blood and urine mercury levels increase correspondingly with the number of amalgams and amalgam surfaces in the mouth. Confirmation of an elevated body burden of mercury can be made by measuring urinary mercury, after provocation with 2,3,-dimercapto-propane sulfonate (DMPS) and this was measured in 150 patients. Apo-E genotyping warrants investigation as a clinically useful biomarker for those at increased risk of neuropathology, including AD, when subjected to long-term mercury exposures. Additionally, when clinical findings suggest adverse effects of chronic mercury exposure, a DMPS urine mercury challenge appears to be a simple, inexpensive procedure that provides objective confirmatory evidence. An opportunity could now exist for primary health practitioners to help identify those at greater risk and possibly forestall subsequent neurological deterioration.

The term mid-flexion instability has entered the orthopaedic literature as a concept, but has not been confirmed as a distinct clinical entity. The term is used freely, sometimes as a synonym for flexion instability. However, the terms need to be clearly separated. A cadaver study published in 1990 associated joint line elevation with decreased stability at many angles of flexion, but that model was not typical of clinical scenarios. The literature is considered and it is proposed that the more common entity of an uncorrected flexion contracture after a measured resection arthroplasty technique is more likely to produce clinical findings that suggest instability mid-flexion. It is proposed that the clinical scenario encountered is generalised instability, with the appearance of stability in full extension from tight posterior structures. This paper seeks to clarify whether mid-flexion instability exists as an entity distinct from other commonly recognised forms of instability.

Background Implant overdentures are one of the most common treatment options used to rehabilitate edentulous patients. Attachment systems are used to anchor the overdentures to implants. The plethora of attachment systems available dictates a need for clinicians to understand their prosthodontic and patient‐related outcomes. Objectives To compare different attachment systems for maxillary and mandibular implant overdentures by assessing prosthodontic success, prosthodontic maintenance, patient preference, patient satisfaction/quality of life and costs. Search methods Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 24 January 2018); Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 12) in the Cochrane Library (searched 24 January 2018); MEDLINE Ovid (1946 to 24 January 2018); and Embase Ovid (1980 to 24 January 2018). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials on 24 January 2018. No restrictions were placed on the language or date of publication when searching the electronic databases. Selection criteria All randomised controlled trials (RCTs), including cross‐over trials on maxillary or mandibular implant overdentures with different attachment systems with at least 1 year follow‐up. Data collection and analysis Four review authors extracted data independently and assessed risk of bias for each included trial. Several corresponding authors were subsequently contacted to obtain missing information. Fixed‐effect meta‐analysis was used to combine the outcomes with risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (95% CI). We used the GRADE approach to assess the quality of evidence and create 'Summary of findings' tables. Main results We identified six RCTs with a total of 294 mandibular overdentures (including one cross‐over trial). No trials on maxillary overdentures were eligible. Due to the poor reporting of the outcomes across the included trials, only limited analyses between mandibular overdenture attachment systems were possible. Comparing ball and bar attachments, upon pooling the data regarding short‐term prosthodontic success, we identified substantial heterogeneity (I2 = 97%) with inconsistency in the direction of effect, which was unexplained by clinical or methodological differences between the studies, and accordingly we did not perform meta‐analyses for this outcome. Short‐term re‐treatment (repair of attachment system) was higher with ball attachments (RR 3.11, 95% CI 1.68 to 5.75; 130 participants; 2 studies; very low‐quality evidence), and there was no difference between both attachment systems in short‐term re‐treatment (replacement of attachment system) (RR 1.18, 95% CI 0.38 to 3.71; 130 participants; 2 studies; very low‐quality evidence). It is uncertain whether there is a difference in short‐term prosthodontic success when ball attachments are compared with bar attachments. Comparing ball and magnet attachments, there was no difference between them in medium‐term prosthodontic success (RR 0.84, 95% CI 0.64 to 1.10; 69 participants; 1 study; very low‐quality evidence), or in medium‐term re‐treatment (repair of attachment system) (RR 1.75, 95% CI 0.65 to 4.72; 69 participants; 1 study; very low‐quality evidence). However, after 5 years, prosthodontic maintenance costs were higher when magnet attachments were used (MD ‐247.37 EUR, 95% CI ‐346.32 to ‐148.42; 69 participants; 1 study; very low‐quality evidence). It is uncertain whether there is a difference in medium‐term prosthodontic success when ball attachments are compared with magnet attachments. One trial provided data for ball versus telescopic attachments and reported no difference in prosthodontic maintenance between the two systems in short‐term patrix replacement (RR 6.00, 95% CI 0.86 to 41.96; 22 participants; 1 study; very low‐quality evidence), matrix activation (RR 11.00, 95% CI 0.68 to 177.72; 22 participants; 1 study; very low‐quality evidence), matrix replacement (RR 1.75, 95% CI 0.71 to 4.31; 22 participants; 1 study; very low‐quality evidence), or in relining of the implant overdenture (RR 2.33, 95% CI 0.81 to 6.76; 22 participants; 1 study; very low‐quality evidence). It is uncertain whether there is a difference in short‐term prosthodontic maintenance when ball attachments are compared with telescopic attachments. In the only cross‐over trial included, patient preference between different attachment systems was assessed after only 3 months and not for the entire trial period of 10 years. Authors' conclusions For mandibular overdentures, there is insufficient evidence to determine the relative effectiveness of different attachment systems on prosthodontic success, prosthodontic maintenance, patient satisfaction, patient preference or costs. In the short term, there is some evidence that is insufficient to show a difference and where there was no evidence was reported. It was not possible to determine any preferred attachment system for mandibular overdentures. For maxillary overdentures, there is no evidence (with no trials identified) to determine the relative effectiveness of different attachment systems on prosthodontic success, prosthodontic maintenance, patient satisfaction, patient preference or costs. Further RCTs on edentulous cohorts must pay attention to trial design specifically using the same number of implants of the same implant system, but with different attachment systems clearly identified in control and test groups. Trials should also determine the longevity of different attachment systems and patient preferences. Trials on the current array of computer‐aided designed/computer‐assisted manufactured (CAD/CAM) bar attachment systems are encouraged.

Abstract Pasture mealybug ( Balanococcuspoae ) was found infesting two field trials evaluating the performance of selected strains of the endophyte Neotyphodium lolii in ryegrass ( Lolium spp.) in Canterbury, New Zealand. Deterioration of endo‐phyte‐free plots relative to endophyte‐infected plots had been observed. In Trial A, pasture mealybug were sampled in plots of the perennial ryegrass cultivar ‘Grasslands Nui’, without endophyte (nil), or infected with the wild‐type endophyte, or the selected strains, AR1 and AR37. In Trial B, mealybug numbers on six ryegrass cultivars infected with AR1 or wild‐type were compared with those on the same cultivars without endophyte. In sampling these trials, the presence of a root aphid, Aploneura lentisci , was also noted. Populations of mealybug in both trials were similar on all endophyte‐infected treatments and significantly lower than populations on nil treatments. Neither AR1 nor wild‐type appeared to reduce root aphid numbers, while AR37 may have had some effect. The amount of dead grass was significantly greater in nil than in endophyte‐infected plots in Trial A, and yield of ryegrass was correlated with numbers of mealybug and root aphid present. Pasture productivity in nil treatments had recovered by spring, in the year of the outbreak. The presence of endophyte, strain of endophyte and cultivar were all significant factors affecting both total dry matter and green yield in Trial B. Pasture mealybug accounted for 55% of the variation in a decline in growth rate that occurred in this trial over the summer‐autumn periods between 2000 and 2001, particularly in the nil treatments. Two years after the outbreak there was 25% less ryegrass and persistently lower pasture yields in nil plots. We conclude that pasture mealybug are capable of inflicting severe damage to endophyte‐free ryegrass in Canterbury, particularly during dry summer‐autumn periods.