Timing of two versus three doses of quadrivalent HPV vaccine and associated effectiveness against condyloma in Sweden: a nationwide cohort study.

OBJECTIVE: To assess incidence of condyloma after two doses of quadrivalent human papillomavirus (qHPV) vaccine, by time since first vaccine dose, in girls and women initiating vaccination before age 20 years. DESIGN: Register-based nationwide open cohort study. SETTING: Sweden. PARTICIPANTS: Girls and women initiating qHPV vaccination before age 20 years between 2006 and 2012. The study cohort included 264 498 girls, of whom 72 042 had received two doses of qHPV vaccine and 185 456 had received all three doses. MAIN OUTCOME MEASURE: Incidence rate ratios (IRRs) of condyloma estimated by time between first and second doses of qHPV in months (m) and age at vaccination, adjusted for attained age. RESULTS: For girls first vaccinated with two doses before the age of 17 years, the IRR of condyloma for 0-3 months between the first and second doses was 1.96 (95% CI 1.43 to 2.68) as compared with the standard three-dose schedule. The IRRs were 1.27 (95% CI 0.63 to 2.58) and 4.36 (95% CI 2.05 to 9.28) after receipt of two doses with 4-7 months and 8+ months between doses, respectively. For women first vaccinated after the age of 17 years, vaccination with two doses of qHPV vaccine and 0-3 months between doses was associated with an IRR of 2.12 (95% CI 1.62 to 2.77). For an interval of 4-7 months between doses, the IRR did not statistically significantly differ to the standard three-dose schedule (IRR=0.81, 95% CI 0.36 to 1.84). For women with 8+ months between dose 1 and dose 2 the IRR was 3.16 (95% CI 1.40 to 7.14). CONCLUSION: A two-dose schedule for qHPV vaccine with 4-7 months between the first and second doses may be as effective against condyloma in girls and women initiating vaccination under 20 years as a three-dose schedule. Results from this nationwide study support immunogenicity data from clinical trials.

Incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease after quadrivalent human papillomavirus vaccination: a cohort study.

OBJECTIVE: To assess whether quadrivalent human papillomavirus (qHPV) vaccination is associated with increased incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease. METHODS: This register-based open cohort study included all girls and women between 10 and 30 years of age in Sweden in 2006-2012 diagnosed with at least one of 49 prespecified autoimmune diseases (n = 70 265). Incidence rate ratios were estimated for new-onset autoimmune disease within 180 days of qHPV vaccination using Poisson regression adjusting for, country of birth, parental country of birth, parental income and parental education. RESULTS: A total of 70 265 girls and women had at least one of the 49 predefined autoimmune diseases; 16% of these individuals received at least one dose of qHPV vaccine. In unvaccinated girls and women, 5428 new-onset autoimmune diseases were observed during 245 807 person-years at a rate of 22.1 (95% CI 21.5-22.7) new events per 1000 person-years. In vaccinated girls and women, there were 124 new events during 7848 person-years at a rate of 15.8 (95% CI 13.2-18.8) per 1000 person-years. There was no increase in the incidence of new-onset autoimmune disease associated with qHPV vaccination during the risk period; on the contrary, we found a slightly reduced risk (incidence rate ratio 0.77, 95% CI 0.65-0.93). CONCLUSION: In this nationwide study, qHPV vaccination was not associated with increased incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease.

Expression of the nuclear transport protein importin ß-1 and its association with the neurokinin 3 receptor in the rat hypothalamus following acute hyperosmotic challenge.

The tachykinin NK3 receptor (NK3R) is a G-protein coupled receptor that is activated, internalized, and trafficked to the nuclei of magnocellular neurons in the paraventricular nucleus of the hypothalamus (PVN) in response to acute hyperosmolarity. The lack of information on the nuclear import pathway raises concerns about the physiological role of nuclear NK3R. NK3R contains a nuclear localizing sequence (NLS) and this raises the possibility that importins are involved in transport of NK3R through the nuclear pore complex. The following experiments utilized: (1) co-immunoprecipitation to determine if NK3R is associated with importin ß-1 following activation in response to acute hyperosmolarity in vivo, and (2) immuno-neutralization of importin ß-1 in vitro to determine if nuclear transport of NK3R was blocked. Rats were given an i.v. injection of hypertonic saline (2 M) and 10 min after the infusion, the PVN was removed and homogenized. Importin ß-1 co-immunoprecipitated with the NK3R following treatment with 2 M NaCl, but not following isotonic saline treatment. Immuno-neutralization of importin ß-1 decreased the transport of NK3R into the nuclei in a time dependent fashion. The results indicate that in response to acute hyperosmotic challenge, NK3R associates with importin ß-1 which enables the nuclear transport of NK3R. This is the first in vivo study linking importin ß-1 and the nuclear transport of a G protein coupled receptor, the NK3R, in brain.

Anticoagulation intensity sufficient for haemodialysis does not prevent activation of coagulation and platelets.

BACKGROUND: A single bolus of dalteparin at the start of haemodialysis (HD) may prevent clot formation, but subclinical activation of platelets and coagulation may still occur. Consequently, the relationship between clinical clotting events and activation markers of platelets and coagulation before and during HD is of interest. METHODS: The effect of tapered doses of dalteparin during 84 HD sessions (4-4.5 h) was prospectively examined in 12 patients. Six of the patients were treated with warfarin. The initial dalteparin dose was reduced to 50% if no clotting was observed. Clinical clotting was evaluated by inspection of the air trap every hour and by inspection of the dialyser after each session. Anti-FXa activity was measured for assessment of dalteparin activity. Markers of activated plasma coagulation, (thrombin-antithrombin (TAT) and prothrombin fragment 1+2 (PF1+2)) and a marker of platelet activation (beta-thromboglobulin, beta-TG), were measured before the start of and after 3 and 4 h of dialysis. Ten pre-dialytic patients with chronic renal failure served as a control group. A total of 230 measurements of each parameter were performed. RESULTS: An anti-FXa activity above 0.4 IU/ml at the end of HD inhibits overt clot formation for 4 h. This was obtained by an intravenous dalteparin dose of about 5000 IU. TAT and PF1+2 correlated to clinical clotting episodes (r=0.50 and 0.47, P<0.001). beta-TG was not significantly correlated to clinical clotting. All parameters increased during the sessions (TAT, PF1+2, beta-TG, P<0.001). When measurements during clinical clotting episodes were disregarded, all parameters were still markedly increased. Warfarin-treated patients had lower TAT and PF1+2. Dialysis patients had higher beta-TG values than pre-dialytic patients. CONCLUSION: Despite clinically effective anticoagulation, obtained by dalteparin administration, platelets and coagulation are activated by HD, resulting in a potentially thrombophilic state. Warfarin treatment reduces clinical clot formation and subclinical activation of coagulation.

A single dose of dalteparin effectively prevents clotting during haemodialysis.

BACKGROUND: A single bolus dose of LMW heparin at the start of haemodialysis effectively prevents clot formation in the dialyser and bubble trap. However, there are few studies on the appropriate dosage of LMW heparins in haemodialysis. Therefore we examined the relationship between the anticoagulant effect of dalteparin and clinical clotting during haemodialysis. METHODS: We performed an open, prospective study on the effect of decreasing doses of dalteparin in 12 haemodialysis patients during a total of 84 sessions (4-4.5 h). The normally applied dose of dalteparin in each patient was reduced by 25% for each session down to 50% of initial dose if no clotting was observed. Clinical clotting (grade 1-4) was evaluated by visual inspection after blood draining of the air trap every hour and by inspection of the dialyser after each session and compared to corresponding values for anti-FXa activity and dialysis time. Blood flow and ultrafiltration rate were kept within narrow limits throughout the study. RESULTS: No episodes of grade 4 clotting occurred, and no session was interrupted. Eighteen episodes of grade 3 clinical clotting (11%) were observed in patients without warfarin treatment, none with an anti-FXa activity >0.43 IU/ml. Oral warfarin treatment reduced the clinical clotting, and only one grade 3 episode was observed in patients on warfarin therapy. Anti-FXa activity and haemodialysis time were the only factors independently correlated to clotting in a logistic regression model. CONCLUSION: An anti-FXa activity above 0.4 IU/ml after 4 h of dialysis inhibits significant clotting during haemodialysis. A bolus dose of dalteparin of 70 IU/kg usually seems appropriate, but may be reduced in patients on warfarin treatment. Dialysis time is an independent risk factor for clinical clotting.

A new protocol for the transmission of physiological signals by digital telemetry.

A method has been devised to transmit physiological signals from the brains of rats using a new digital telemetry transmission protocol. The chief advantage of the present system over existing systems is that the circuit only consumes power during the transmission of a brief pulse of information. This results in a very much extended battery life allowing the device to be implanted and recordings to be carried out over a longer period of time.

Family planning practices before and after childbirth in Lusaka, Zambia.

A total of 408 randomly selected normally delivered women who had given birth to healthy infants were recruited from a postnatal ward at the University Teaching Hospital (UTH) in Lusaka, Zambia. Family planning practices before and after pregnancy and delivery were investigated among 376 of these women. The interviews were conducted in their homes or at the postpartum clinic at the UTH at the end of puerperium. The remaining 32 women, mainly primiparae, were lost to follow-up. Thirty four percent of the women had used a family planning method before the present childbirth. Most of those (90%) had used modern methods. Women with eight and more years of education used modern contraceptive methods more often than those with less education. One year after delivery, 64% of the women were using modern or traditional family planning methods. Of those who used traditional methods, 15% relied on lactational amenorrhoea. Of those who did not use any method, 39% indicated that their husbands did not allow them. Fifty-six per cent of the teenagers stated that they had no knowledge of family planning, whereas 84% of the single teenagers had not used contraceptives before. In view of this, teenagers and single mothers need a special focus in the development of family planning programmes. We also recommend that more research should focus on views of both men and women on contraceptive use.

PIP: This article presents an analysis of contraceptive usage before and after childbirth among 376 women (out of a total of 408 randomly selected women) delivering at the University Teaching Hospital in Lusaka, Zambia, during 1989-90. 90% of the original 408 women were married and living with their husbands. 75% lived in the high-density districts of Lusaka. 60% were housewives, and 22% had regular wage employment. 80% of husbands had regular paid employment. 66% reported knowledge of at least one contraceptive method; 34% had no contraceptive knowledge. 97% of those with some knowledge knew about modern methods. 56% of adolescents were unaware of any contraceptive method. 67% did not use any contraceptives. Of the 33% who used a method, 90% used a modern one. 84.4% of unmarried teenagers had not used contraceptives before the study. 58.4% stopped contraceptive use in order to conceive. After 1 year, 64% of 309 women were using contraceptives, of which 55% used a modern method. The most commonly used method was the pill. 17% of the 89 women who used traditional methods relied on lactational amenorrhea. 92% were still breast feeding (2-11 feeds in a 24-hour period) at the end of a year. 47% were menstruating. 68% had resumed sexual relations. 39% of the women at the end of the year who did not use contraception reported that husbands did not allow this practice. 22 women reported that their infant died within the year. Women with 8 or more years of education were more likely to use modern contraception. Contraceptive knowledge and use was influenced by parity, education, marital status, and age. Women mainly asked about what contraceptive methods were available, when to start use, and where to obtain contraception.

Utilisation of reproductive health services in rural Vietnam; are there equal opportunities to plan and protect pregnancies?

STUDY OBJECTIVES: To describe the utilisation of reproductive health services (family planning, antenatal care, and delivery services) and the socioeconomic determinants for utilisation of health services. DESIGN: This was a cross sectional survey, using a multistage sampling technique. SETTING: Tien Hai district, Thai Binh Province, Vietnam. Altogether 1132 mothers with children under 5 years of age were interviewed about antenatal, delivery, and family planning services utilisation during a five year period (1987-92). MAIN RESULTS: Seventy per cent of the women used contraceptive methods, with the intrauterine device being the most common. The use of the intrauterine device was positively associated with the number of children alive but not with other sociodemographic factors in the mothers. Thirty per cent of the women had attended an antenatal clinic for check ups during their last pregnancy. It was found that mothers with fewer deliveries, higher education, and who were Buddhist or of no religion had utilised antenatal services more frequently than the others. Seventy five per cent of the mothers in this study had been assisted by health professionals at their last delivery. Those mothers with fewer deliveries, higher education, who were Buddhist or had no religion, and had sufficient to eat were more likely to have their births attended by health professionals. CONCLUSIONS: In spite of a relatively high education level in the population and services which are generally available, there was an under utilisation of antenatal and delivery care and there was no equal opportunity for different groups of mothers to use these services. Family planning services were, however, frequently used and were used to the same extent by different groups of mothers. Except for abortion, alternatives to the intrauterine device method were rarely available. If pregnancies are to be protected in an efficient way in rural Vietnam, reproductive health care must be strengthened and efforts should be made to reach the women who are not using these services at present.

An ultrastructural study of the articular cartilage in calcium pyrophosphate dihydrate (CPPD) crystal deposition disease (chondrocalcinosis articularis).

An ultrastructural study of articular cartilage from five patients with calcium pyrophosphate dihydrate (CPPD) crystal deposition disease was performed. The CPPD crystals, identified by micro X-ray diffraction, were usually found in clusters, located in intercellular areas of the intermediate cartilage layer. The matrix surrounding the clusters either showed a normal morphology or a homogeneous appearance, within which faint cross striations but no distinctly fibrillar outlines could be identified. Another change in the matrix, characterized by an increased electron density and longitudinally fragmented collagen fibres, was also seen. This latter change was generally seen without concomitant CPPD crystal deposition. No specific relationship between the crystals and the collagen fibres or the granular background material of the matrix was encountered.

[Abortion and contraception information during first period under new legislation]. / Abort- och preventivmedelsrådgivning under första kvartalet med ny lagstiftning

PIP: The frequency of abortion and contraceptive counseling in the first 3 months of 1975 under the new Swedish abortion law is compared with previous trends in abortion and counseling. The number of abortions in the 1st quarter of 1975 indicates a yearly increase of 8% in the number of abortions performed with relation to 1974. The number of teen-age abortions in the 1st quarter of 1975 was approximately 25% of the total. 90% of the cases were performed by vacuum aspiration, and 85% were performed before the 13th week of pregnancy. Based on the figures for these 3 months, 83,500 government subsidized contraceptive counseling visits took place, compared with 500,000 for the entire year 1974. This rather modest figure for 1975 is a result of a new organization of the counseling system, with large increases in some geographic and decreases in others. Private physicians have been reducing services in this field as a result of the standard government compensation for contraceptive counseling. It is felt that the capacity for increased counseling will be realized during 1975.^ieng