Is gambling an emerging public health issue for Wales, UK?

BACKGROUND: Not all gambling exposes people to the same level of harm. Harm from gambling is found at the individual, social (family and friends) and community levels. This includes financial hardship, psychological distress and interpersonal conflict or relationship breakdown. The harm from gambling to wider society includes fraud, theft, loss of productivity in the workforce and the cost of treating this addiction. The annual estimated excess cost of gambling for Wales is between £40 and £70 million. METHODS: This study reviews the existing data sources and literature to ascertain if gambling is an emerging public health issue in Wales. RESULTS: In Wales 61% of adults had gambled in the last year (1.5 million people). And 1.1% of the population (30 000 people) self-report as having a problem with gambling using either the Problem Gambling Severity Index or the Diagnostic and Statistical Manual of American Psychiatric Association tools. The 'ripple effect' of gambling harm can mean friends and family are highly impacted. CONCLUSION: The existing data and literature together with the rapidly evolving developments in infrastructure demonstrate that gambling is an emerging public health issue in Wales. The impact on families and society warrants population level interventions to tackle this public health issue.

Use of a 40-day rolling incidence to monitor pertussis in Nova Scotia, 2015.

BACKGROUND: Pertussis can cause a serious respiratory bacterial infection, especially in infants. Between January 1 and December 31, 2015, there was an increase in the number of reported pertussis cases in Nova Scotia (NS). Surveillance practices for pertussis in NS were challenging because immunization coverage data are not available and rate information was neither timely nor precise with respect to geography. Public health officials in NS decided to adopt a new surveillance technique to inform public health actions across the Province. OBJECTIVE: To assess the use of a 40-day rolling incidence rate to monitor pertussis activity in Nova Scotia. INTERVENTION: A 40-day rolling incidence rate was calculated for pertussis by age groups and various levels of geography. Public health authorities continued to anticipate new cases of pertussis if the contacts of known cases were still within the incubation period (range between six and 20 days). The 40-day incubation period was chosen to reflect twice the incubation period's upper range. Rates were calculated using Statistics Canada population projections for 2014 and then compared with traditional case counts and cumulative incidences. The usefulness of the statistics was assessed by public health decision makers. OUTCOMES: Increased pertussis activity was noted across NS, most notably in the South West region. The use of a 40-day rolling incidence rate as a surveillance tool provided more timely and geographically precise descriptions of ongoing trends in pertussis activity and helped to inform appropriate public health action. Health officials valued the information provided from the rolling incidence because it allowed them to manage activities based on weekly estimates at various levels of geography. CONCLUSION: Rolling incidence proved to be a useful tool to monitor a cyclical increase in pertussis cases in Nova Scotia and to inform related public health actions. The rolling incidence provided geographically precise and timely information that was useful to estimate new cases in the absence of reliable immunization coverage information. This method could supplement traditional epidemiological surveillance of future communicable disease events, especially those characterized by long incubation periods and low case counts.

Translocated dogs from Nunavut and the spread of rabies.

BACKGROUND: Investigations of rabid animals that cross provincial/territorial boundaries are resource intensive and complex because of their multi-jurisdictional and multi-sectoral nature. OBJECTIVE: To describe the multi-jurisdictional responses to two unrelated rabid puppies originating from Nunavut. METHODS: A descriptive summary of the investigations following the identification of a rabid puppy in Alberta (August 2013) and another in Saskatchewan (December 2014). RESULTS: These investigations involved public health and agriculture authorities in five provinces/territories, as well as the Canadian Food Inspection Agency (CFIA). In Alberta, a puppy who became ill after being transported by air from Nunavut was euthanized and diagnosed with rabies (Arctic fox variant). Eighteen individuals were assessed for exposure to rabies; nine received rabies post-exposure prophylaxis (RPEP). An exposed household dog that tested negative was electively euthanized. In Nunavut, the rabid puppy's mother and litter mates were placed under quarantine. In Saskatchewan, another puppy became ill during transit by air from Nunavut. It was subsequently euthanized and diagnosed with rabies (Arctic fox variant). Two of three Saskatchewan individuals, including a veterinary technician, received RPEP. Two Nova Scotia residents were exposed to the puppy while in Nunavut and received RPEP. One household dog received booster vaccination, was quarantined for 45 days and remained asymptomatic. In Nunavut, the rabid puppy's mother and litter mates were not identified. In both cases, exposure to an Arctic fox was the probable source of rabies in the puppies. CONCLUSION: Translocation of dogs from the north where Arctic fox rabies is endemic poses a risk to human and animal health and may negatively impact control of rabies in Canada. There is currently no national framework to prevent inter-jurisdictional movement of potentially rabid animals in Canada.

Improving service quality: experience from the Tanzania Family Health Project.

OBJECTIVE: To improve the quality and uptake of reproductive health service in rural communities in Tanzania. DESIGN: Descriptive study of operational research. SETTING: One and a half million people living in urban and rural communities in the Mbeya Region of Tanzania. METHOD: Design and implementation of a range of service quality improvement measures. INTERVENTIONS: Management systems strengthening; clinical skills training; orientation of health staff to service quality; introduction of quality assurance systems; improvement to supervision systems; community involvement in monitoring health service delivery. OUTCOME MEASURES: Health service utilization rates; client perceptions of health service quality; situation analysis of health service provision. RESULTS: Uptake of reproductive health services increased; improved client perceptions of service quality; improved health infrastructure; increased community participation in health service management. CONCLUSIONS: Health service quality in sub-Saharan Africa can be improved substantially through a process of identifying and addressing the constraints which militate against effective service provision. The cost of such improvement is modest compared with current health expenditure. Health planners and managers involved in sectoral reform programmes should give due attention to quality assurance mechanisms in addition to structural elements of the reform process.

An outbreak of waterborne cryptosporidiosis associated with a public water supply in the UK.

In November and December 1992, an outbreak of waterborne cryptosporidiosis occurred in Bradford, a city in the North of England. In all 125 cases were involved, the majority of whom lived in part of the city which received its drinking water supply from a single water treatment works. A case control study demonstrated an association between illness and the consumption of tapwater from this source; those drinking large volumes being more likely to have been ill. Treated water from the defined source yielded cryptosporidial oocysts. Heavy rainfall was recorded in the catchment area of the reservoir supplying raw water to the treatment works, immediately prior to the probable time of infection, based on dates of onset of illness.

Psychological morbidity and the availability of assisted conception: a group comparison study.

BACKGROUND: Given its limited availability, it is worth while to explore the relationship between the non-availability of assisted conception and psychological morbidity among subfertile women, to see if those denied the procedure experience poorer health. METHODS: A non-randomized group comparison study was carried out in Bradford Health Authority, England. Sixty-six women who had reached the point at which assisted conception was deemed appropriate, but for whom such treatments were not available, were compared with 49 parous women, and 73 newly diagnosed subfertile women. The General Wellbeing Index (GWI) was used to measure their psychological wellbeing. RESULTS: Cases and subfertile controls have similar levels of wellbeing, whereas parous controls have significantly higher average levels than cases. This pattern is seen in the simple unadjusted comparison and also when adjustments are made for the distributions of age, life event score and social class. CONCLUSIONS: Subfertile women experience poorer psychological health than similar parous women. Subfertile women, for whom assisted conception is an appropriate but unavailable treatment option, appear to have similar psychological health to those who are being investigated and treated by other means.

Iodine deficiency disorders in Dowa District

This study was carried out to serve as preliminary study for a possible wider population survey on the prevalence of iodine deficiency disorders. The results indicate that there is iodine deficiency in the pupils attending three schools in the three areas investigated. The high prevalence of both total goitre (65 percent) and visible goitre (8 percent) among the children; seems to indicate that areas of severe endemicity could exist in Dowa District

Iodine deficiency disorders (I.D.D.): a survey in Dowa District

In June 1990; a survey was carried out to give a preliminary impression of the degree of prevalence of iodine deficiency disorders in Dowa district. Results show that areas included in the study suffer from moderately severe iodine deficiency; there is a high prevalence of goitre; female children are more at risk; the long term soloution of adding iodine to all salth sold in the country would be likely to be of benefit

Synthesis and structure-activity relationships of antibacterial phosphonopeptides incorporating (1-aminoethyl)phosphonic acid and (aminomethyl)phosphonic acid.

Phosphonodipeptides and phosphonooligopeptides based on L- and D-(1-aminoethyl)phosphonic acids L-Ala(P) and D-Ala(P) and (aminomethyl)phosphonic acid Gly(P) at the acid terminus have been synthesized and investigated as antibacterial agents, which owe their activity to the inhibition of bacterial cell-wall biosynthesis. A method for large-scale synthesis of the potent antibacterial agent L-Ala-L-Ala(P) (1, Alafosfalin) is described. Structure-activity relationships in the dipeptide series have been studied by systematic variation of structure 1. L stereochemistry is generally required for both components. Changes in the L-Ala(P) moiety mostly lead to loss of antibacterial activity, but the phosphonate analogues of L-phenylalanine, L-Phe(P), and L-serine, L-Ser(P), give rise to weakly active L-Ala-L-Phe(P) and L-Ala-L-Ser(P). Replacement of L-Ala in 1 by common and rare amino acids can give rise to more potent in vitro antibacterials such as L-Nva-L-Ala(P) (45). Synthetic variation of these more potent dipeptides leads to decreased activity. Phosphonooligopeptides such as (L-Ala)2-L-Ala(P) have a broader in vitro antibacterial spectrum than their phosphonodipeptide precursor, but this is not expressed in vivo, presumably due to rapid metabolism to 1. Stabilized compounds such as Sar-L-Nva-L-Nva-L-Ala(P) (46) have been developed that are more potent in vivo and have a broader in vivo antibacterial spectrum than the parent phosphonodipeptide.

Phosphonopeptides as substrates for peptide transport systems and peptidases of Escherichia coli.

Peptide transport and peptidase susceptibility of the antibacterial agent alafosfalin and other phosphonopeptides have been characterized in Escherichia coli. Phosphonodipeptides were accumulated by a process which appeared to involve multiple permeases; saturation was not achieved even at concentrations of 128 microM. Competition studies showed that these compounds had only a low affinity for the system transporting phosphonooligopeptides and were rapidly taken up by and were inhibitory to E. coli mutants unable to transport the toxic peptide triornithine. Phosphonodipeptides containing D-residues were not appreciably transported. By contrast, phosphonooligopeptides were generally transported by a distinct saturable permease system for which they had a high affinity. This system was identical to that utilized by triornithine. Phosphonooligopeptides with simple monoalkyl substituents at the amino terminus were also transported except in the case of a t-butyl substituent. The oligopeptide permease was also able to transport certain derivatives which contained some residues having D rather than L stereochemistry. Intracellular metabolism of phosphonooligopeptides was initiated almost exclusively by hydrolysis from the N terminus by an L-specific peptidase. This initial hydrolytic activity was unaffected by the aminopeptidase inhibitor bestatin, unlike the final hydrolysis step which yields L-1-aminoethylphosphonic acid from the phosphonodipeptide intermediate.

Antibacterial activity and mechanism of action of phosphonopeptides based on aminomethylphosphonic acid.

Phosphonopeptides based on aminomethylphosphonic acid as the C-terminal residue linked to L-amino acids possessed antibacterial activity in vitro and in vivo. Analogs in this series were generally less potent than corresponding compounds based on L-1-aminoethylphosphonic acid such as alafosfalin (L-alanyl-L-1-aminoethylphosphonic acid). Significant differences in antibacterial spectra were observed. The mechanism of action involved active transport of the peptide mimetics into the bacterial cells, followed by intracellular release of high concentrations of aminomethylphosphonic acid which inhibited bacterial cell wall biosynthesis. Aminomethylphosphonic acid behaved as a mimetic of both D- and L-alanine and inhibited D-Ala-D-Ala synthetase (EC 6.3.2.4.), alanine racemase (EC 5.1.1.1.), and UDP-N-acetylmuramyl-L-alanine synthetase (EC 6.3.2.8.). The minimal inhibitory concentration of L-norvalyl-aminomethylphosphonic acid was essentially unaffected by the presence of D-alanine, whereas the activity of the corresponding L-norvalyl derivative of L-1-aminoethylphosphonic acid was markedly decreased. Substantial differences in the inhibitory and lytic activity of the L-norvalyl derivatives of aminomethylphosphonic and L-1-aminoethylphosphonic acids were also observed when these agents were combined with other inhibitors of bacterial cell wall biosynthesis.

Antibacterial properties of alafosfalin combined with cephalexin.

The phosphonopeptide alafosfalin (L-alanyl-L-1-aminoethylphosphonic acid) exhibited synergy in vitro and in animal studies against a range of bacterial genera when combined with cephalexin. Alafosfalin also showed synergy with mecillinam and, to a much lesser extent, with ampicillin. Synergy with cephalexin was more pronounced when the bacteria were relatively insensitive to the beta-lactam component. The action of this combination involved both an inhibitory and a bacteriolytic mechanism which was abolished by concurrent treatment with the aminopeptidase inhibitor, bestatin. Regrowth of subpopulation resistant to either component was markedly reduced by the combination. The potential of alafosfalin combined with cephalexin for use in therapy is discussed.

Phosphonopeptide antibacterial agents related to alafosfalin: design, synthesis, and structure-activity relationships.

Dipeptide variants of alafosfalin (L-alanyl-L-1-aminoethylphosphonic acid) with substantial differences in potency and antibacterial spectrum in vitro and in vivo have been synthesized. Certain dipeptides with alternatives to the L-alanyl residue had broader antibacterial spectra; activity against Pseudomonas aeruginosa was included. Some compounds had better in vivo activity than alafosfalin when introduced into infected rodents orally, but for the majority of the more active phosphonodipeptides, parenteral administration was more effective. Certain oligopeptides derived from the more active phosphonodipeptides possessed good in vitro activity against an extended range of organisms; they included Haemophilus influenzae, Streptococcus faecalis, and Streptococcus pneumoniae. The in vivo activity of some of these phosphono-oligopeptides was significantly greater than that of the parent dipeptide and correlated well with the in vitro results. This indicates that phosphono-oligopeptides exert part of their in vivo action directly, in addition to that arising from smaller peptides produced by peptidase cleavage.

Phosphonopeptides as antibacterial agents: alaphosphin and related phosphonopeptides.

Alaphosphin, l-alanyl-l-1-aminoethylphosphonic acid, was selected from a range of phosphonopeptides for evaluation in humans on the basis of its antibacterial activity, pharmacokinetics, and stability to intestinal and kidney peptidases. In vitro, the antibacterial action was antagonized by small peptides, resulting in low activity on peptone media. On an antagonist-free medium alaphosphin was bactericidal and rapidly lysed most susceptible gram-negative bacteria, but it was largely bacteriostatic and essentially nonlytic against gram-positive organisms. Its spectrum included most strains normally isolated from urinary tract infections, but potency was greatly reduced by very high inoculum levels and by alkaline pH. Although strains of Proteus and Pseudomonas were less susceptible to alaphosphin than were other common gram-negative bacteria, like other species they formed spheroplasts when exposed under appropriate conditions. Alaphosphin was equally effective against penicillin-susceptible and -resistant strains and showed no cross-resistance with known antibiotics. Good synergy and increased bactericidal activity were demonstrated with combinations of alaphosphin and d-cycloserine or beta-lactam antibiotics.

Phosphonopeptides as antibacterial agents: rationale, chemistry, and structure-activity relationships.

Peptide mimetics with C-terminal residues simulating natural amino acids have been designed as inhibitors of bacterial cell wall biosynthesis. The phosphonopeptide series consisting of various l and d residues of natural amino acids combined with 1-aminoalkyl (and aryl-alkyl-) phosphonic acid residues had the most interesting antibacterial properties when the C-terminal residue was l-1-aminoethylphosphonic acid. The in vitro antibacterial activities of representative phosphonodi- to phosphonohexapeptides were investigated. The antibacterial action of the active compounds has been explained in terms of transport into the bacterial cell and intracellular release of the alanine mimetic, which interferes with the biosynthesis of the peptidoglycan of the bacterial cell wall.

Phosphonopeptides as antibacterial agents: mechanism of action of alaphosphin.

The novel antibacterial peptide mimetic alaphosphin (l-alanyl-l-1-aminoethylphosphonic acid) selectively inhibited peptidoglycan biosynthesis in both gram-negative and gram-positive bacteria. It induced accumulation of uridine diphosphate-N-acetyl-muramyl-tripeptide in gram-positive organisms and significantly reduced the intracellular pool levels of d-alanine. Alaphosphin was actively transported into bacterial cells by stereospecific peptide permeases and was subsequently hydrolyzed by intracellular aminopeptidases to yield l-1-aminoethylphosphonic acid. This alanine mimetic rapidly accumulated inside susceptible cells to yield a concentration which was 100- to 1,000-fold in excess of that of the precursor peptide in the surrounding medium. In the case of susceptible gram-negative organisms, it was shown that 1-aminoethylphosphonic acid was incorporated into a metabolite which was tentatively identified as uridine diphosphate-N-acetylmuramyl-aminoethylphosphonate. The primary intracellular target site of 1-aminoethylphosphonic acid was alanine racemase (EC 5.1.1.1), which was reversibly and competitively inhibited in the gram-negative organisms Escherichia coli and Pseudomonas aeruginosa and irreversibly inhibited in a time-dependent manner in the gram-positive organisms Staphylococcus aureus and Streptococcus faecalis. A secondary target site could be uridine diphosphate-N-acetylmuramyl-l-alanine synthetase [EC 6.3.2.8(b)]. The mechanism of action of alaphosphin may be regarded as involving at least three stages: (i) active transport by peptide permeases; (ii) intracellular peptidase cleavage; and (iii) action of l-1-aminoethylphosphonate on alanine racemase.