The use of oral appliances in obstructive sleep apnea: a retrospective cohort study spanning 14 years of private practice experience.

PURPOSE: In 2005, the American Academy of Sleep Medicine stated, "Oral appliances are indicated for use in patients with mild to moderate obstructive sleep apnea (OSA) who prefer them to CPAP therapy, or who do not respond to, are not appropriate candidates for, or who fail treatment attempts with CPAP." However, this recommendation is based upon variable results from only six studies with more than 100 participants. These studies have assessed the effectiveness of mandibular advancement devices (MADs) in specific groups (military populations, academic institutions, or hospital settings) with no large study conducted in a fee-for-service private practice where the majority of patients receive MADs for OSA. The purpose of this study is to report outcomes of a board-certified dental sleep practitioner managing mild, moderate, and severe OSA using customized titratable MADs. We hypothesize that patients will demonstrate a significant reduction in apnea-hypopnea index (AHI) scores after adjusting their customized titratable MADs. METHODS: This is a 14-year retrospective study design with pre- and post-treatment sleep studies. An AHI score < 10 respiratory events per hour with therapy is defined as treatment success. This study was performed by a single private practitioner. RESULTS: Of 2419 patient records analyzed, 544 (22%) had pre- and post-treatment sleep studies (89% polysomnograms). Of 510 patients with complete data, 459 (90%) revealed a decrease in AHI score < 10 respiratory events per hour indicating treatment success. Only 51 of these patients (10%) had a final AHI ≥ 10 and were considered treatment failures. Among the patients who lacked post overnight polysomnogram, 66/1921 (3%) discontinued the MAD due to adverse effects. Considering these patients as treatment failures as well, and therefore adding their number to the patients with complete sleep study data, the total treatment failures were 117/576 or 20%. Of the treatment successes, OSA was categorized by AHI at baseline as mild in 170 (34%), moderate in 181 (36%), and severe in 138 (28%). CONCLUSIONS: In patients with evaluable data, there was an 80% success rate for treatment of OSA using a custom-fabricated adjustable MAD including substantial numbers of patients with moderate and severe disease.

Sleep and sensorimotor integration during early vocal learning in a songbird.

Behavioural studies widely implicate sleep in memory consolidation in the learning of a broad range of behaviours. During sleep, brain regions are reactivated, and specific patterns of neural activity are replayed, consistent with patterns observed in previous waking behaviour. Birdsong learning is a paradigmatic model system for skill learning. Song development in juvenile zebra finches (Taeniopygia guttata) is characterized by sleep-dependent circadian fluctuations in singing behaviour, with immediate post-sleep deterioration in song structure followed by recovery later in the day. In sleeping adult birds, spontaneous bursting activity of forebrain premotor neurons in the robust nucleus of the arcopallium (RA) carries information about daytime singing. Here we show that, in juvenile zebra finches, playback during the day of an adult 'tutor' song induced profound and tutor-song-specific changes in bursting activity of RA neurons during the following night of sleep. The night-time neuronal changes preceded tutor-song-induced changes in singing, first observed the following day. Interruption of auditory feedback greatly reduced sleep bursting and prevented the tutor-song-specific neuronal remodelling. Thus, night-time neuronal activity is shaped by the interaction of the song model (sensory template) and auditory feedback, with changes in night-time activity preceding the onset of practice associated with vocal learning. We hypothesize that night-time bursting induces adaptive changes in premotor networks during sleep as part of vocal learning. By this hypothesis, adaptive changes driven by replay of sensory information at night and by evaluation of sensory feedback during the day interact to produce the complex circadian patterns seen early in vocal development.

Alemtuzumab (anti-CD52 monoclonal antibody) as single-agent therapy in patients with relapsed/refractory chronic lymphocytic leukaemia (CLL)-a single region experience on consecutive patients.

Alemtuzumab, a humanized anti-CD52 monoclonal antibody, is used in patients with refractory chronic lymphocytic leukaemia (CLL). We report results in health care with alemtuzumab on consecutive, advanced-stage patients from a well-defined geographical region. Records from 1,301 patients (Stockholm-Cancer-Registry 1991-2010) identified 56 relapsed/refractory patients treated with alemtuzumab. Median age was 69 years, 88 % had advanced Rai-stage with median 3 prior therapies. One fourth had bulky lymphadenopathy and 73 % were refractory to purine analogues. Median treatment length was 11.6 weeks. Median cumulative dose was 930 mg, significantly higher (p = 0.0277) for responders. Overall response-rate (ORR) was 43 %; 32.5 %, 50 % and 87.5 % in the Refractory, Purine analogue relapsed and Relapsed/Other subgroup, respectively. Response rate was significantly associated with subgroup (p = 0.0104). Good performance status (PS) was associated with better response rate (p = 0.0227). Median time-to-treatment-failure (TTF) (months) was 7.8 months, significantly (p < 0.0001) longer for responders (13.4) Major infections occurred in 36 %. Median overall survival was 22.5 months (range 0.4-74.3). Positive predictive factors were good PS (p < 0.0001) and fewer previous therapies (p = 0.0038). Twenty percent were retreated with alemtuzumab with an ORR of 54.5 %, and a TTF of 7.1 months. A high cumulative dose/longer duration of therapy and a relatively high response rate was observed compared to previous reports. Optimal patient identification and management may result in avoidance of early discontinuation and possibly better outcomes.

Mammalian-like features of sleep structure in zebra finches.

A suite of complex electroencephalographic patterns of sleep occurs in mammals. In sleeping zebra finches, we observed slow wave sleep (SWS), rapid eye movement (REM) sleep, an intermediate sleep (IS) stage commonly occurring in, but not limited to, transitions between other stages, and high amplitude transients reminiscent of K-complexes. SWS density decreased whereas REM density increased throughout the night, with late-night characterized by substantially more REM than SWS, and relatively long bouts of REM. Birds share many features of sleep in common with mammals, but this collective suite of characteristics had not been known in any one species outside of mammals. We hypothesize that shared, ancestral characteristics of sleep in amniotes evolved under selective pressures common to songbirds and mammals, resulting in convergent characteristics of sleep.

Defining the patterns of PAP adherence in pediatric obstructive sleep apnea: a clustering analysis using real-world data.

STUDY OBJECTIVES: The implementation of positive airway pressure (PAP) therapy to treat obstructive sleep apnea in children is a complex process. PAP therapy data are highly heterogeneous in pediatrics, and the clinical management cannot be generalized. We hypothesize that pediatric PAP users can be subgrouped via clustering analysis to guide tailored interventions. METHODS: PAP therapy data for 250 children with obstructive sleep apnea were retrospectively examined using unsupervised hierarchical cluster analysis based on (1) PAP tolerance (average hours on days used) and (2) consistency of PAP use (percentage of days used). Clinical features in each cluster were defined, and a tree decision analysis was generated for clinical implementation. RESULTS: We were able to subclassify all 250 children (median age = 11.5 years) into five clusters: A (13.6%), B (29.6%), C (17.6%), D (16.4%), and E (22.8%). The clusters showed significant differences in PAP use patterns (Kruskal-Wallis P value < 1e-16). The most consistent PAP use patterns were seen in clusters A, B, and C. Major differences across clusters included the prevalence of obesity, PAP setting, developmental delay, and adenotonsillectomy. We also identified important differences in mask acceptance, OSA severity, and individual responses to PAP therapy based on objective apnea-hypopnea reductions in PAP downloads. CONCLUSIONS: A simple method to subset PAP use patterns in children can be implemented by analyzing cloud-based PAP therapy data. This novel approach may contribute to optimization of PAP therapy in children of all ages based on real-world evidence at the individual level.

Alarming spread of vancomycin resistant enterococci in Sweden since 2007.

The total number of persons infected or colonised with vancomycin-resistant enterococci mandatorily reported to the Swedish Institute for Infectious Disease Control increased dramatically during 2007 and 2008. During a period of twenty months from 1 July 2007 to 28 February 2009, a total of 760 cases were reported compared with 194 cases reported during the entire period from 2000 to 2006. This rise was mainly attributed to a wide dissemination of vancomycin resistant enterococci which started in a number of hospitals in Stockholm in the autumn of 2007 and was followed by dissemination in various healthcare facilities (hospitals and homes for the elderly) in a further two Swedish counties in 2008. The majority of the cases (97%) were acquired in Sweden and among these, healthcare-acquired E. faecium vanB dominated (n=634). The majority of these isolates had identical or closely related pulsed-field gel electrophoresis patterns indicating clonal dissemination in the affected counties. The median minimum inhibitory concentration of vancomycin was 32 mg/L (ranging from 4 to >128 mg/L) and of teichoplanin 0.12 mg/L (ranging from 0.06 to 0.25 mg/L). Particular emphasis was placed on countermeasures such as screening, contact tracing, cleaning procedures, education in accurate use of infection control practices as well as increasing awareness of hygiene among patients and visitors. With these measures the dissemination rate decreased substantially, but new infections with the E. faecium vanB strain were still detected.

Efficacy of partner notification for Chlamydia trachomatis among young adults in youth health centres in Uppsala County, Sweden.

BACKGROUND: The study was conducted to define the contact-tracing success rate of the partner notification services routinely provided by the community-based youth health centres and the county medical officer for communicable disease control (CMO) in Uppsala County, Sweden. OBJECTIVE: The study had three goals, (i) to register the number of sexual partners routinely reported by each diagnosed index case with CT and the success rate in tracing and testing these partners for CT infection. (ii) To analyse the current notification practices in reporting the number of cases of unsuccessful contact tracing to the CMO. (iii) To determine the contact tracing success rate of the partner notification services provided by the CMO. METHODS: Each diagnosed case of CT is obliged by law to participate in the contact-tracing procedure performed by the physician managing the patient or by a specialised sexually transmitted infection (STI) adviser. Successful contact-tracing is defined as the confirmed attendance of a sexual contact within 12 months of the contact with the index case. RESULTS: The number of CT cases diagnosed by the youth health centres during the study period was 463 (299 females and 164 males). The females reported 660 male sexual contacts and the males reported 386 female contacts. Successful partner notification was achieved for 73% of all sexual contacts. 284 (190 females and 94 males) unsuccessful partner notifications were reported to the CMO of whom 98 (52%) of the female contacts and 20 (21%) of the male contacts were successfully notified by the CMO. However, for 134 (71 females and 63 males) partners, personal details given by the index case were insufficient for identification of the partner. CONCLUSIONS: When asymptomatic, genital CT infection spreads among sexually active young adults with multiple, unidentified sexual partners, appropriate methods of partner notification are not sufficient to achieve its aims at the population level.

Extensive transmission of an isoniazid-resistant strain of Mycobacterium tuberculosis in Sweden.

SETTING: City of Stockholm, Sweden. BACKGROUND: The incidence of tuberculosis (TB) in Sweden increased by 40% between 2003 and 2005. The spread of a unique TB strain resistant to isoniazid (INH) contributed to this increase. OBJECTIVE: To describe outbreaks of TB caused by this single strain, elucidate possible causes for its extensive spread and identify shortcomings of the TB control programme in Sweden. RESULTS: We identified a cluster consisting of 102 culture-confirmed TB cases with identical DNA fingerprints and 26 epidemiologically related cases, not confirmed by culture, all diagnosed between 1996 and 2005. Five partly separate outbreaks of this strain were discovered. Epidemiological links were established for 56% of the culture-confirmed cases and for all cases not confirmed by culture. Three patients died while receiving treatment, four became failures and eight defaulted or were lost to follow-up. Only eight patients received directly observed treatment (DOT) up to a period of 3 months, although 40% had poor adherence. CONCLUSIONS: Shortcomings of the national TB programme were revealed. Improved contact tracing and case holding, including DOT, is crucial to reduce TB transmission in Sweden.

Divergent anti-HBc reactivities in HB-immune and chronic HBsAg carriers.

We have monitored titers of anti-HBc antibodies in sera from acutely HBV-infected and chronic HBsAg carriers. Our data show that there is a divergence in the specificity of the antibodies in these two populations. We also present preliminary results showing that serum from HB-immune carriers contain antibodies that are multispecific and display autoimmune characteristics, reacting with human serum albumin.

HBcAg induced T-cell independent anti-HBc production in chronic HBsAg carriers.

The capacity of the nucleocapsid protein of HBV to function as a T-cell independent antigen in man was studied. When T-cell depleted B-cell cultures were challenged with E coli-derived HBcAg, anti-HBc production was registered in culture supernatants from the majority of chronic HBsAg carriers in a quiescent stage of disease. In contrast, similarly prepared and stimulated cultures from donors with natural acquired immunity to hepatitis B or HB-susceptible controls were non-responsive. Addition of autologous T-cells effectively restored anti-HBc responsiveness in T-cell depleted B-cell cultures from HB-immune donors, demonstrating the T-cell dependency for anti-HBc induction in natural HBV-infection.

Clonal analysis of Streptococcus pneumoniae nonsusceptible to penicillin at day-care centers with index cases, in a region with low incidence of resistance: emergence of an invasive type 35B clone among carriers.

The nasopharyngeal carriage rate of potential respiratory pathogens was studied in 36 index children with a pneumococci nonsusceptible to penicillin (PNSP), in 595 healthy children, and in 123 personnel at 16 day-care centers (DCCs) with index cases in the Stockholm area, an urban area with a low incidence of antibiotic resistant pneumococci, during the winter of 1997-1998. The spread and clonality of PNSP, Haemophilus influenzae and Moraxella catarrhalis, were studied by analyzing antibiotic susceptibility and serotype, and for PSNP also by using pulsed-field electrophoresis (PFGE) and multilocus sequence typing (MLST). In contrast to the low carriage rate found among the adult contacts (2%), 40% of the children harbored pneumococci, of which 20% were PNSP. Nasopharyngeal colonization decreased with age. The 49 PNSP isolates consisted of 20 clones, of which 10 could be identified in more than one child attending the same or different DCCs. In five DCCs, we observed a spread of PNSP from the index case. A novel PNSP clone of type 35B, found to cause invasive disease in several states in the United States, was found to emerge among several carriers at two DCCs . A high proportion of PNSP isolates were multiresistant to antibiotics (34%), which has implications for treatment regimens, even in a country like Sweden where the proportion of PNSP currently is low (3-4%). One PNSP clone of type 9V found among the carriers, has been shown to cause invasive disease in Sweden as well as in other countries, suggesting that one reason for the occurrence of invasive PNSP clones may be their ability to colonize and spread among healthy carriers. Other internationally spread antibiotic resistant pneumococcal clones found were of types 9V, 19F, and 23F.

Drug-resistant Streptococcus pneumoniae in day-care centres in Stockholm County.

Between January 1994 and July 1995, 40 pre-school children were found to have drug-resistant Streptococcus pneumoniae(DRSP), i.e. reduced sensitivity to penicillin (minimum inhibitory concentration, MIC, > or =0.1) and resistance to at least two other antibiotic drugs. Twenty-five of the children were index cases with symptoms of respiratory disease, and 15 children were carriers discovered in contact-tracing in connection with an index case. Children attending the same group in the day-care centre as an index child were routinely screened. Thirteen of the index children were attending day-care centres. In 11 of these day-care centres, contact-tracing and nasopharyngeal swabs from 424 children and 128 day-care personnel identified an additional 13 asymptomatic children who were carriers of DRSP. In all but one case, the same serotype as the index case was discovered. No day-care personnel were carriers of the DRSP strain. Sixteen (64%) of the 25 children with symptoms caused by DRSP were 1 year old or younger, whereas eight (61%) of the 13 children who were carriers of DRSP were 3-4 years old. In conclusion, when a child attending a day-care centre is discovered to have respiratory disease caused by DRSP, there is a great probability that additional children will be identified in the group with the same DRSP strain.

[WHO spearheads global initiative to eradicate hepatitis B]. / WHO leder globalt initiativ för att utrota hepatit B.

It is estimated that over 350 million people live with a chronic hepatitis B virus (HBV) infection, claiming over one million deaths per year due to progress of the chronic disease to cirrhosis and/or hepatocellular carcinoma (HCC). An extended program of immunization including hepatitis B vaccine for children under one year of age has been launched in more than 110 countries. Recent studies conclude that mass hepatitis B immunization is effective in preventing HBV infection and has resulted in a decrease in the occurrence of HCC in children living in countries where hepatitis B is endemic. However, the vast majority of infected children live in the poorest developing countries in Africa and Asia that currently cannot afford the vaccine or lack the basic infrastructure necessary to deliver a national immunization service. The Global Alliance for Vaccines and Immunization (GAVI) was established in 1999 as an alliance of WHO, UNICEF, the World Bank, industry, foundations, and other partners to reinvent immunization for the 21st century, by forging a common vision and new ways of working together at global, regional and national levels. WHO recommends global elimination of hepatitis B by universal infant and/or adolescent immunization, but health planners in Sweden and the other Scandinavian countries, the Netherlands and UK have not yet been convinced of the cost-effectiveness of HB-prevention through routine childhood immunization with HB-vaccine. The inclusion of hepatitis B vaccine in already available multivalent vaccines may alter this situation in the future, but until then an intensified vaccination strategy aimed at those groups of individuals that are particularly at risk for hepatitis B should be adopted in accordance with the recommendations of The Swedish National Board of Health (SOSFS 1991:2) and local instructions from the County Medical Officer for Communicable Disease Control.

[Specimen culture from all children in a day care center because of an outbreak of streptococcal infection]. / Odling på samtliga barn vid streptokockutbrott i förskola.

In an outbreak of recurrent group A streptococcal (GAS) pharyngotonsillitis between January and February 1997 at a Swedish preschool, involving 58% (11/19) of the children and several family members, clinical examination showed few of the children to manifest signs and symptoms of tonsillitis. However, throat specimens yielded GAS growth of the same T-type in 42% (8/19) of the children and in 30% (6/20) of family members, but in none of the staff. Strict hygiene, appropriate antibiotic treatment of all culture-positive individuals irrespective of symptoms, and non-attendance at the preschool during the first two days of treatment promptly terminated the outbreak and there were no cases of recurrence.

[Evaluation of the law of communicable disease control: compulsory isolation can reduce the high-risk behavior of HIV-positive individuals]. / Utvärdering av smittskyddslagen: tvångsisolering kan minska HIV-smittades högriskbeteende.

The Swedish approach to HIV is based on HIV-positive individuals' fulfilling their societal obligation to prevent further spread of the disease. Under section 38 of the Communicable Disease Act of 1989, compulsory admission to hospital may be resorted to in cases where voluntary efforts have failed to bring about modification of high-risk behaviour. The article consists in a report of a retrospective study of the effects of such enforced isolation in the HIV-positive subgroup committed under the Act within an eight-year period. Relevant information was obtained from the records of medical and psychiatric hospitals, the social services and correctional care authorities. Modification of high-risk behaviour was assessed by enquiries involving attending physicians, the social services, and prison and police authorities, and by interviews with the patients. During the 8-year period, 1.5 per cent (44/2982) of registered HIV-positive patients in Stockholm County were committed by the county administrative court to compulsory admission. Of the 44 patients, 25 (57%) were born in Sweden, and 19 (43%) elsewhere (mostly sub-Saharan African countries where HIV is highly endemic). Intravenous drug abuse was very common in the subgroup, and 34 per cent of them were diagnosed as having a psychiatric disorder or intellectual handicap. Thirty-four (77%) of the subgroup were released after varying periods of isolation. Follow-up at 6, 18 and 36 months showed the overwhelming majority to be capable of maintaining a low-risk profile, and only 20 per cent to be characterised by continued high-risk behaviour (suspected or verified). The results thus suggest that individuals with the intellectual and psychiatric capacity to comprehend the serious nature of HIV infection and its modes of transmission can successfully modify risk behaviour by undergoing intensified individualised programmes, provided the duration of isolation is sufficiently long.

Prevalence trends in Sweden for the new variant of Chlamydia trachomatis.

In 2006, a new variant of Chlamydia trachomatis (nvCT) was discovered in Sweden that was not detectable with Abbott m2000 (Abbott) and Amplicor/COBAS Amplicor/TaqMan48 (Roche). The proportion of nvCT was 20-64% of the detected Chlamydia cases in counties using Abbott/Roche test systems. Although the ProbeTec system from Becton Dickinson (BD) could detect nvCT, the proportion of nvCT in counties using BD was 7-19%. The objective of the current study was to follow the nvCT proportions from 2007 to 2009 in two counties that used Roche and had introduced test systems able to detect nvCT in late 2006. The nvCT was also followed in two counties that used BD, and in all four counties the effect of nvCT on the serotype distribution of C. trachomatis wild-type strains was analysed. A total of 2576 specimens positive for C. trachomatis were collected in the four counties at three time points, and analysed for nvCT and serotype E. The proportion of nvCT declined significantly in the two counties using Roche, from 65% and 48% in 2007 to 24% for both counties in 2009 (p <0.001). The nvCT proportion increased in Norrbotten county, which used BD, from 9% in 2007 to 19% in 2009 (p 0.03). In Uppsala county, which also used BD but was surrounded by counties using detection systems from Roche, the proportion of nvCT declined from 24% in 2007 to 18% in 2009 (p <0.03). No major difference in the level of serotype E was seen. The proportion of nvCT seems to rapidly converge in the Swedish counties after the selective diagnostic advantage for nvCT has been lost in the Abbott/Roche counties.