Pilot randomized controlled trial evaluating the effect of random nicotine delivery on cigarettes per day and smoke exposure.

BACKGROUND: Many smokers report attempting to quit each year, yet most relapse, in part due to exposure to smoking-related cues. It is hypothesized that extinction of the cue-drug association could be facilitated through random nicotine delivery (RND), thus making it easier for smokers to quit. The current study aimed to evaluate the effects of RND on smoking cessation-related outcomes including cigarettes per day (CPD) and exhaled carbon monoxide (CO). METHODS: Participants were current smokers (>9 CPD) interested in quitting. Novel trans-mucosal, orally dissolving nicotine films, developed by Bionex Pharmaceuticals, were used in the study. The pharmacokinetic profile of these films was assessed in single (Experiment 1) and multiple-dose (Experiment 2) administrations prior to the smoking cessation study (Experiment 3). In Experiment 3, participants were randomized 1:1:1 to recieve 4 nicotine films per day of either: placebo delivery (0 mg), steady-state delivery (2 mg), or random nicotine delivery (RND) (0 mg or 4 mg). After two weeks, participants were advised to quit (target quit date, TQD) and were followed up 4 weeks later to collect CPD and CO and to measure dependence (Penn State Cigarette Dependence Index; PSCDI) and craving (Questionnaire of Smoking Urges; QSU-Brief). Means and frequencies were used to describe the data and repeated measures ANOVA was used to determine differences between groups. RESULTS: The pharmacokinetic studies (Experiment 1 and 2) demonstrated that the films designed for this study delivered nicotine as expected, with the 4 mg film delivering a nicotine boost of approximately 12.4 ng/mL across both the single and the multiple dose administration studies. The films reduced craving for a cigarette and were well-tolerated, overall, and caused no changes in blood pressure or heart rate. Using these films in the cessation study (Experiment 3) (n = 45), there was a significant overall reduction in cigarettes smoked per day (CPD) and in exhaled CO, with no significant differences across groups (placebo, steady-state, RND). In addition, there were no group differences in dependence or craving. Adverse events included heartburn, hiccups, nausea, and to a lesser extent, vomiting and anxiety and there were no differences across groups. CONCLUSION: Overall, this pilot study found that RND via orally dissolving films was feasible and well tolerated by participants. However, RND participants did not experience a greater reduction in self-reported CPD and exhaled CO, compared with participants in the steady-state and placebo delivery groups. Future studies to evaluate optimal RND parameters with larger sample sizes are needed to fully understand the effect of RND on smoking cessation-related outcomes.

A case of gastric cancer after sleeve gastrectomy.

There is concern over how to survey the remnant upper gastrointestinal tract, as well as what to do if a patient subsequently develops an upper gastrointestinal cancer following bariatric surgery. We hereby report a case of gastric cancer arising 8 years after a laparoscopic sleeve gastrectomy (LSG). The patient, a 42 year-old woman, was diagnosed with a gastric cancer via esophagogastroduodenoscopy (EGD). As such, she underwent a laparoscopic total gastrectomy with lymphadenectomy. The final histopathology was that of a poorly differentiated adenocarcinoma with signet-ring cells without lymph node metastases (staging pT4aN0). The background gastric mucosa displayed no Helicobacter pylori. There have only been a few reported cases of gastric cancer after sleeve gastrectomy. Nevertheless, it may be wise to consider performing EGD at regular intervals after bariatric surgery, especially in Asia. In this regard, LSG holds an advantage over Roux-en-Y gastric bypass with respect to the feasibility of surveillance of the remnant stomach.

International prospective observational study of upper gastrointestinal haemorrhage: Does weekend admission affect outcome?

INTRODUCTION: Out of hours admissions have higher mortality for many conditions but upper gastrointestinal haemorrhage studies have produced variable outcomes. METHODS: Prospective study of 12 months consecutive admissions of upper gastrointestinal haemorrhage from four international high volume centres. Admission period (weekdays, weeknights or weekends), demographics, haemodynamic parameters, laboratory results, endoscopy findings, further procedures and 30-day mortality were recorded. Five upper gastrointestinal haemorrhage risk scores were calculated. RESULTS: 2118 patients, 60% male, median age 66 years were studied. Compared with patients presenting on weekdays, patients presenting at weekends had no significant differences in comorbidity, pulse, systolic BP, risk scores, frequency of peptic ulcers or varices. Those presenting on weekdays had lower haemoglobin (p = 0.007) and were more likely to have a normal endoscopy (p < 0.01). Time to endoscopy was less for weeknight presentation (p = 0.001). Sixty-seven per cent of those presenting on weekdays, 75% on weeknights and 60% at weekends had endoscopy within 24 h. Transfusion requirements, need for endoscopic therapy or surgery/embolization, rebleeding rates (6.1%) and mortality (7.2%) did not differ with presentation time. CONCLUSION: This multi-centre international study in large centres found no difference in demographics, comorbidity or haemodynamic stability and no increase in mortality for patients presenting with upper gastrointestinal haemorrhage out of hours.

[Failure to Attend Child Preventive Examination as a Possible Indication of Risk to Children's Welfare: Retrospective Analysis of 605 Cases Reported to the Child Protection Services]. / Nicht-Teilnahmen an Kindervorsorgeuntersuchungen als Indiz für Kindeswohlgefährdung? ­ Eine retrospektive Analyse von 605 an das Jugendamt gemeldeten Fällen.

Objective: The extent to which childrens's welfare is compromised when they do not attend compulsory prevention medical check-ups is yet to be determined. Together with the Hessen Prevention Center for Children (Hessisches Kindervorsorgezentrum), the Child Protection Services in the Main-Taunus district have conducted a study to investigate failure to attend child preventive examinations as a possible indication of risk to the welfare of such children. Method: 605 notifications of child preventive examinations that were not carried out, sent in 2012 to the Child Protection Services by the Hessen Prevention Center for Children, were analyzed retrospectively. Each case was recorded using a standardized questionnaire and, cases that were passed on to General Social Services within Child Protection Services were investigated with an additional interview with the employee responsible. Results: In 60 (10%) cases there was no certificate to show that the check-up had been conducted, while in 165 (27%) cases the check-up was conducted late, i. e. only after being contacted by the Child Protection Services. In 9 of the 605 cases (1.5%), the families involved were already known to Child Protection Services due to previous proceedings against them under endangering children's welfare act (known as § 8a cases). No new case of a risk to children's welfare was detected. In 58 cases, families gave reasons for the missed or late check-up. Reasons included being abroad and moving house (20 cases), forgetting (14 cases) and illness (11 cases), as well as lack of knowledge of the law (6 cases), lack of health insurance (4 cases), lack of language skills (2 cases) and objection to the law in principle (1 case). It was notable that, in 57% of the cases notified, documentary evidence could be provided by the end of the case work that the check-up had taken place within the recommended period (including additional discretionary period). The majority of these notifications of failure to attend can be prevented by an upstream clearing procedure.

[Status quo of children's preventative medicine programmes--results of the first German nationwide workshop 2011 in Frankfurt am Main]. / Zum aktuellen stand der kindervorsorgeprogramme--ergebnisse des ersten bundesweiten arbeitstreff ens 2011 in Frankfurt am Main.

10 of the 13 federal states presented their structures, implementation methods and results as part of the nationwide workshop for children's preventative medicine and early recognition projects for Germany on 9th September 2011 in Frankfurt am Main. This was the first time a full overview of all programmes of this kind in Germany has been possible. The programmes and data from these 10 presentations were analysed and compared. Despite the many differences between the legal frameworks and structural implementation, the programmes also displayed similarities in the implementation and in the problems which arise. Significantly improved participation rates for early recognition check-ups have been achieved in the context of the programmes. Previously, only a few detailed evaluations for the detection of risks to children's welfare and other effects such as vaccination rates and improvements in children's health through more advice and care were available.

Beneficial use of steroids in hereditary neuropathy with liability to pressure palsy.

Management of hereditary neuropathy with liability to pressure palsy (HNPP) is primarily conservative, aimed at preventing nerve injury by avoiding trauma or other potential aggravating factors. No pharmacological treatment is known to be beneficial. We describe two adolescents, one with HNPP (male; aged 15y) and another with a clinical picture suggestive of HNPP (genetically unconfirmed; female; aged 14y), who showed considerable improvement of their symptoms after receiving corticosteroid therapy. Both individuals were symptomatic for at least 5 months before the treatment. Following corticosteroids, both individuals demonstrated rapid improvement leading to near-complete recovery of muscle power. Clinical improvement after corticosteroid therapy has been reported in some individuals with other hereditary neuropathies. Our cases demonstrate that corticosteroid therapy may also be beneficial in individuals with HNPP who have a protracted or incomplete course of recovery.

Effect of surfactants and pH on naltrexone (NTX) permeation across buccal mucosa.

The objective of this pre-formulation study was to systematically investigate the effects of two surfactants (Brij 58(®) and Tween 80(®)) and change in solution pH on in vitro permeation of naltrexone HCl (NTX-HCl) across tissue engineered human buccal mucosa. For the study, 10mg/ml solutions of Tween 80(®) (0.1 and 1%, w/v) and Brij 58(®) (1%, w/v) were prepared in standard artificial saliva buffer solution (pH 6.8). For studying pH effects, solution pH was adjusted to either 7.5 or 8.2. As controls, three concentrations of NTX-HCl (2.5, 10 and 25mg/ml) were prepared. Using NTX standard solution (10mg/ml; pH 6.8), the permeation was observed between in vitro human and ex vivo porcine mucosa. It was observed that Brij 58(®) increased the permeation rates of NTX significantly. The flux of 10mg/ml solution (pH 6.8) increased from 1.9 ± 0.6 (× 10(2)) to 13.9 ± 2.2 (× 10(2))µg/(cm(2)h) (approximately 6-fold) in presence of 1% Brij 58(®). Increasing pH of NTX-HCl solution was found to increase the drug flux from 1.9 ± 0.6 (× 10(2)) (pH 6.8) to 3.0 ± 0.6 (× 10(2)) (pH 7.4) and 8.0 ± 3.5 (× 10(2)) (pH 8.2)µg/(cm(2)h), respectively. Histological analyses exhibited no tissue damage due to exposure of buccal tissue to Brij 58(®). The mean permeability coefficients (K(p)) for 2.5, 10 and 25mg/ml solutions of NTX-HCl (pH 6.8) were 5.0 (× 10(-2)), 1.8 (× 10(-2)) and 3.2 (× 10(-2))cm/h, respectively, consistent with data from published literature sources. Increase of NTX flux observed with 1% Brij 58(®) solution may be due to the effects of ATP. Increase in flux and the shortening of lag time observed by increasing in solution pH confirmed earlier finding that distribution coefficient (logD) of NTX is significantly affected by small increments in pH value and therefore plays an important role in NTX permeation by allowing faster diffusion across tissue engineered human buccal tissue.

[Pediatric tibial fractures: is conservative therapy still currently appropriate?]. / Kindliche Unterschenkelfrakturen: Ist die Konservative Therapie zeitgemäss?

Leg-length inequality is the most common complication reported after pediatric tibial fractures. We reviewed 196 patients with tibial fractures. The mean age at the time of fracture was 7.6 years (range 10 months-12 years). In all, 176 patients were treated conservatively, 162 by immediate cast bracing and 14 by skeletal traction. In 20 patients the fracture was stabilized by osteosynthesis. Thirteen patients were treated by plate fixation; in 4 fractures located in the distal third of the tibia, we used crossed Kirschner wires. In one case we used a screw osteosynthesis; another distal fracture was stabilized by a fibula rushpin, and in one third-degree open fracture an arthrodesis of the upper ankle joint was necessary. A total of 71 patient were interviewed and examined. All were skeletally mature at the time of reexamination. A leg-length discrepancy was found in 40 patients. Shortening of 5-15 mm had occurred in 11 patients; 29 patients had experienced lengthening of 5-20 mm. In 21 patients, leg-length discrepancy was more than 5 mm (13 had lengthening of 10-20 mm, 8 had shortening of 10-15 mm). Leg-length discrepancy was significantly higher in patients younger than 10 years (P = 0.024, chi 2-test according to Pearson). The number of repositions also played an important role (1 or more; P = 0.006). With fibula involvement, leg-length discrepancy was significantly higher (P = 0.018). Both factors indicate the grade of fracture instability. The authors conclude that conservative treatment of pediatric tibial fractures is still appropriate. However, instable fractures as well as fractures in children > 10 years of age should be operated upon primarily.

[Endoscopic therapy of adnexa tumors using endobag extraction]. / Endoskopische Therapie von Adnextumoren unter Verwendung der Endobag-Extraktion.

Evidence of 39 treated cases of cystic adnexal tumours of unclarified quality indicates that laparoscopic resection with subsequent extraction of the entire tumour in an endobag could provide the possibility of an endoscopic operation even in cases of indistinct tumours or of patients with enhanced perioperative risks. In particular patients with increased morbidity due to immobilisation might especially benefit from the technique.

[Disorders of growth and development in patients with osteogenesis imperfecta and their effects on the orofacial system]. / Wachstums- und Entwicklungsstörungen bei Patienten mit Osteogenesis imperfecta und deren Auswirkungen auf das oro-faziale System.

The results of stomatological examinations covering 16 children with osteogenesis imperfecta are reported. This disease is accompanied by typical symptoms in the oro-facial region. Dentinogenesis imperfecta occurred in 5 patients and can be considered an optional symptom of osteogenesis imperfecta.

[Tooth and jaw development in the Silver-Russel syndrome]. / Zahn- und Kieferentwicklung beim Silver-Russel-Syndrom.

The symptoms of Silver-Russel syndrome are described using two cases. Special attention was paid to the development of the teeth and the jaws. The typical microretrognathism is accompanied by a frontal crowding especially in the lower jaw. It is possible to adjust it to a regular occlusion using functional orthopedic appliances. Noticeable is the high degree of caries in the first dentition. Paramorphiae are not ascertainable. Etiologically, the submucosal cleft palate, which was diagnosed for the first time, would suggest an intrauterine disturbance in the eighth to the tenth week of pregnancy.

Seroepidemiology of malaria: age-specific pattern of Plasmodium falciparum antibody, parasite and spleen rates among children in an endemic area in peninsular Malaysia.

A seroepidemiological study was carried out on Orang Asli (Aborigines) children who lead a semi-nomadic life in the deep jungles of Ulu Kelantan, Malaysia. Out of a total of about 190 children below 14 years, 143 were studied. Blood was collected from finger pricks on standard "strip type" filter papers for indirect fluorescent antibody (IFA) tests with Plasmodium falciparum antigen. A positive reaction at 1:10 dilution in infants and young children was considered positive and the reasons are given. The P. falciparum antibody prevalence rate was 84.6% compared to 81.8% spleen and 43.4% parasite rates. Both P. Falciparum and P. vivax were present in children. The age-specific patterns of antibody, spleen and parasite rates were those of a hyperendemic community. There was a positive correlation between antibody and spleen rates up to the age of 9 years. In older children, the antibody rates increased while the spleen and the parasite rates dropped.

Singapore: resumption of rapid fertility decline in 1973.

PIP: Singapore's fertility decline began in the late 1950s, and continued until a record low of 44,562 births in 1969. Subsequently another upswing in the number of births took place, taking a downturn again to 48,269 in 1973. The decline in the crude birthrate in 1973 was entirely caused by a fall in fertility, and was retarded by the fact that there was a rise in the proportion of women in the reproductive ages. Indians and Malays contributed the most to the decline in fertility in 1973, while Chinese fertility only fell 6.6%. Government population legislation and social measures designed to lower the birthrate appear to have noticeably affected reproductive behavior.^ieng

Knowledge, attitudes, and practice of family planning in Singapore.

The First National Survey on Family Planning in Singapore was designed to gather data that would aid in evaluating the program of the National Family Planning and Population Board and the influence of government population policies on attitudes toward family planning. Interviews with 2,078 currently married women aged 15--44 revealed high levels of contraceptive knowledge and use, satisfaction of clinic users with the Board's services, and attitudes that favor greater acceptance of abortion and sterilization. Continued promotion of the concept of the two-child family appears necessary in light of divided opinions of respondents on this government recommendation.

PIP: A KAP survey was conducted in Singapore in 1973 based on the House/Household Listing and Numbering Schedules compiled in the 1970 Population Census. 2945 census houses were selected, and all currently married women aged 15-44 in each selected household were included in the sample. The 2076 eligible women indicated: the appropriate age to marry is 22.6 for women and 26.6 for men; the ideal number of children is 3.1; 69% approve of contraception; 98% have heard of at least one method of contraception, and 77% have at some time practiced contraception; 55% know that abortion is legal in Singapore, and 43% know where it can be obtained; 72% to 96% expressed satisfaction with the government-run family planning program.

The first national survey on family planning in Singapore, 1973.

PIP: Despite the fact that by the end of 1972 191,971 women or about 60% of the population had used the Singapore Family Planning and Population Board's services since its establishment in 1966, the extent of the success of the program cannot be fully assessed and the objectives of future programs properly formulated unless there is reliable and comprehensive data on certain unknown variables. In order to provide this knowledge, a decision was made in April 1973 to conduct the First National Survey on Family Planning in Singapore. The goal was to obtain information concerning the level of family planning phenomena in Singapore in terms of knowledge of attitudes and practice of family planning, legalized abortion, voluntary sterilization as well as the information on knowledge of attitudes toward government population policies and the hard-core nonusers of the services. Concerning methodology, a two stage stratified sample design was used with reticulated housing units forming the primary sampling units and census houses the secondary sampling units. The list of houses used as the sampling frame was obtained from House/Household Listing and Numbering Schedules compiled in the 1970 Population Census. A questionnaire was prepared to collect information on data covering personal characteristics of the respondent and her husband. The fieldwork of the survey was in three phases: a) updating of the sampling frame prior to the selection of census houses; b) the identification of the eligible women for the main surevey, and the interviewing of the eligible women in the main survey itself. Results of the survey indicate that of the 2078 currently married women interviewed, 69% approved of family planning, 11% disapproved, and 19% said "it depends." Regarding induced abortion, 23% approved and 52% disapproved. The ideal family size based on their replies was computed to be 3.1. The survey confirmed that the married women have a good knowledge of family planning methods and that the proportion who have ever practiced birth control reached 77%. Women were generally satisfied with the Board's services, and regarding their attitudes towards government population policies -- it seems that the personal experience of the married women has an important effect on their knowledge of population policies. This has been only a brief account of the survey; however, the detailed results and their implications in terms of new strategies in family planning programmes and population policies will be made available in a full report scheduled to be published in 1974.^ieng