Establishing a valid cohort of patients with acromegaly by combining the National Patient Register with the Swedish Pituitary Register.

PURPOSE: The aim of this study was to establish a valid national cohort of patients diagnosed with acromegaly by combining data from the general National Patient Register (NPR) and the disease-specific Swedish Pituitary Register (SPR). METHODS: Patients ≥ 18 years of age at diagnosis of acromegaly reported from 1991 to 2018 who were registered in the NPR and/or SPR were included. The diagnosis of acromegaly was considered correct for patients identified in both registers or confirmed through chart review. Medical records were reviewed in two of Sweden´s six health care regions if the patient was reported only in the NPR. An algorithm for the NPR, with criteria requiring multiple diagnosis registrations and tumour and/or surgery codes, was constructed to reduce the number of patients to review in the remaining four regions. RESULTS: A total of 1866 patients were identified. Among these, 938 were reported in both registers. After application of the algorithm and chart review, the diagnosis was confirmed for 83 of the 906 patients found only in the NPR. Among 22 patients only registered in the SPR, a review of medical records confirmed acromegaly in 13. This resulted in a total of 1034 cases with acromegaly during the study period. The incidence rate of acromegaly in Sweden 1991-2018 was calculated to 4.0/million/year in the entire population and 5.1/million/year among subjects ≥ 18 years of age. CONCLUSION: The combination of the SPR and NPR established a valid cohort of patients diagnosed with acromegaly and increased the estimated incidence in Sweden.

Validity and reliability of the Swedish version of the Self-Efficacy for Managing Chronic Disease scale for individuals with systemic sclerosis.

OBJECTIVE: To investigate aspects of validity and reliability of the Swedish version of the Self-Efficacy for Managing Chronic Disease (SEMCD-Swe) scale in systemic sclerosis (SSc). METHOD: A forward-backward translation procedure was used. Content validity was assessed through interviews with 11 people with SSc and 10 healthcare professionals. Construct validity, internal consistency, test-retest reliability, and floor and ceiling effects were evaluated in 104 SSc patients. RESULTS: The content validity of the SEMCD-Swe was interpreted as satisfactory, but some adjustments were made to increase the understanding. Confirmatory factor analysis supported a single-factor structure. Moderate to strong correlations between the SEMCD-Swe and Scleroderma Health Assessment Questionnaire; Multidimensional Assessment of Fatigue; Patient Health Questionnaire-8 (rs = -0.4 to -0.7), and RAND-36 subscales (rs = 0.5 to 0.7) were found. Weak correlations were found between SEMCD-Swe and modified Rodnan skin score; and disease severity of peripheral vascular and lung (rs = -0.1 to -0.2) and kidney (rs = 0.1) systems (Medsger severity scale). Cronbach's alpha was sufficient (0.85) and corrected item-to-total correlations were good (≥ 0.50). The intraclass correlation coefficient for the total score was sufficient (0.82). No floor or ceiling effects were found. CONCLUSION: Support for construct validity was indicated, as the SEMCD-Swe in SSc show a single-factor structure and is more strongly associated with pain, fatigue, depressive symptoms, interferences with daily activities, disability, and quality of life than with disease severity. Our results also indicate support for content validity and reliability. However, the responsiveness of the SEMCD-Swe needs to be tested.

Grandmaternal smoking increases asthma risk in grandchildren: A nationwide Swedish cohort.

BACKGROUND: There is growing interest in exposures prior to conception as possible risk factors for offspring asthma. Although partially supported by evidence from limited human studies, current evidence is inconsistent and based on recall of exposure status. OBJECTIVE: We aimed to investigate grandmaternal smoking during pregnancy and the risk of asthma in grandchildren using prospectively collected population-based data. METHODS: Information on grandmaternal and maternal smoking during pregnancy and grandchild use of asthma medications was collected from national Swedish registries. Associations between grandmaternal smoking during pregnancy (10-12 weeks) and asthma medication use in grandchildren were investigated using generalized estimating equations. Ages at which asthma medications were prescribed classified childhood asthma into never, early transient (0-3 years), late onset (3-6 years) and early persistent (0-3 and 3-6 years) phenotypes. RESULTS: From 1982 to 1986, 44 583 grandmothers gave birth to 46 197 mothers, who gave birth to 66 271 grandchildren (born 1996-2010). Children aged 1-6 years had an increased asthma risk if their grandmothers had smoked during pregnancy, with a higher risk for more exposure (10+ cigs/d; adjusted OR 1.23; 1.17, 1.30). Maternal smoking did not modify this relationship. CONCLUSIONS & CLINICAL RELEVANCE: Children had an increased risk of asthma in the first 6 years of life if their grandmothers smoked during early pregnancy, independent of maternal smoking. Importantly, this exhibited a dose-response relationship and was associated with a persistent childhood asthma phenotype. These findings support possible epigenetic transmission of risk from environmental exposures in previous generations.

Efficacy and safety of bariatric surgery for craniopharyngioma-related hypothalamic obesity: a matched case-control study with 2 years of follow-up.

BACKGROUND: Hypothalamic obesity is a devastating consequence of craniopharyngioma. Bariatric surgery could be a promising therapeutic option. However, its efficacy and safety in patients with craniopharyngioma-related hypothalamic obesity remain largely unknown. OBJECTIVES: We investigated the efficacy of bariatric surgery for inducing weight loss in patients with craniopharyngioma-related hypothalamic obesity. In addition, we studied the safety of bariatric surgery regarding its effects on hormone replacement therapy for pituitary insufficiency. METHODS: In this retrospective matched case-control study, we compared weight loss after bariatric surgery (that is, Roux-en-Y gastric bypass and sleeve gastrectomy) between eight patients with craniopharyngioma-related hypothalamic obesity and 75 controls with 'common' obesity during 2 years of follow-up. We validated our results at 1 year of follow-up in a meta-analysis. In addition, we studied alterations in hormone replacement therapy after bariatric surgery in patients with craniopharyngioma. RESULTS: Mean weight loss after bariatric surgery was 19% vs 25% (difference -6%, 95% confidence of interval (CI) -14.1 to 4.6; P=0.091) at 2 years of follow-up in patients with craniopharyngioma-related hypothalamic obesity compared with control subjects with 'common' obesity. Mean weight loss was 25% vs 29% (difference -4%, 95% CI -11.6 to 8.1; P=0.419) after Roux-en-Y gastric bypass and 10% vs 20% (difference -10%, 95% CI -14.1 to -6.2; P=0.003) after sleeve gastrectomy at 2 years of follow-up in patients with craniopharyngioma-related hypothalamic obesity vs control subjects with 'common' obesity. Our meta-analysis demonstrated significant weight loss 1 year after Roux-en-Y gastric bypass, but not after sleeve gastrectomy. Seven patients with craniopharyngioma suffered from pituitary insufficiency; three of them required minor adjustments in hormone replacement therapy after bariatric surgery. CONCLUSIONS: Weight loss after Roux-en-Y gastric bypass, but not sleeve gastrectomy, was comparable between patients with craniopharyngioma-related hypothalamic obesity and control subjects with 'common' obesity at 2 years of follow-up. Bariatric surgery seems safe regarding its effects on hormone replacement therapy.

Tumour recurrence and enlargement in patients with craniopharyngioma with and without GH replacement therapy during more than 10 years of follow-up.

OBJECTIVE: Most patients who have been treated for craniopharyngioma (CP) are GH deficient (GHD). GH replacement therapy (GHRT) may stimulate tumour regrowth; and one of the concerns with long-term GHRT is the risk of tumour progression. Therefore, the objective was to study tumour progression in CP patients on long-term GHRT. DESIGN: Case-control study. PATIENTS AND METHODS: The criteria for inclusion of cases were: i) GHD caused by CP; ii) GHRT >3 years; and iii) regular imaging. This resulted in 56 patients (mean age at diagnosis 25±16 years) with a mean duration of GHRT of 13.6±5.0 years. As controls, 70 CP patients who had not received GHRT were sampled with regard to follow-up, gender, age at diagnosis and initial radiation therapy (RT). RESULTS: The 10-year tumour progression-free survival rate (PFSR) for the entire population was 72%. There was an association (hazard ratio, P value) between PFSR and initial RT (0.13, 0.001) and residual tumour (3.2, 0.001). The 10-year PFSR was 88% for the GHRT group and 57% for the control group. Substitution with GHRT resulted in the following associations to PFSR: GHRT (0.57, 0.17), initial RT (0.16, <0.001), residual tumour (2.6, <0.01) and gender (0.57, 0.10). Adjusted for these factors, the 10-year PFSR was 85% for the GHRT group and 65% for the control group. CONCLUSIONS: In patients with CP, the most important prognostic factors for the PFSR were initial RT and residual tumour after initial treatment. Long-term GHRT did not affect the PFSR in patients with CP.

Células-tronco mononucleares autólogas e proteína óssea morfogenética na cicatrização de defeitos tibiais experimentalmente induzidos em cães / Autologue mononuclear stem cells and morphogenetic bone protein in experimentally induced tibial defect healing in dogs

Avaliou-se a utilização de células-tronco mononucleares (CTM) na cicatrização de defeito ósseo experimental como alternativa aos métodos convencionais, analisando-se o tempo de evolução cicatricial e a presença dessas células no tecido neoformado. Foram utilizados 18 cães, separados em três grupos (G) de seis, e de cada animal foram colhidas células da medula óssea (MO), contadas e analisadas para morfometria, por meio da contagem manual e mielograma. Um defeito ósseo tibial foi então criado cirurgicamente, e a lesão tratada com esponja de gelatina embebida em solução fisiológica (G1), esponja de gelatina embebida com aspirado de MO processado (G2) e esponja de gelatina embebida com aspirado de MO processado e proteína óssea morfogenética (rhBMP-2) (G3). A cicatrização foi então avaliada por estudos radiográficos, e a presença de CTM foi identificada por meio de marcadores nanocristais Qtracker, em microscopia com luz fluorescente, uma semana após a intervenção cirúrgica. Entre as células identificadas pelo marcador, foram encontradas células da linhagem óssea. As avaliações radiográficas demonstram crescimento ósseo acelerado nos animais de G2 e G3. Houve diferenças significativas entre o G1 e G3 em todos os tempos estudados, e entre G1 e G2 nos tempos de 30 e 45 dias. A utilização de CTM adultas suplementadas ou não com rhBMP-2 é alternativa favorável ao crescimento ósseo em defeitos experimentais agudos de tíbia de cães.

Mononuclear stem cells (MSC) were experimentally implanted in bone defect, as an alternative to the conventional methods, in order to evaluate the healing speed, and the presence of these cells in the new-born tissue. Bone marrow (BM) was collected from 18 dogs, and then counted and morphometrically analyzed by manual count and myelogram. The dogs were separated in three groups (G) of six animals each. A tibial bone defect was surgically made in each dog and the wound was treated with gelatin sponge and physiologic solution (G1), gelatin sponge and processed BM (G2), and gelatin sponge, processed BM, and rhBMP-2 (G3). The healing was evaluated by radiographic study and the presence of MSC was microscopically identified by Qtracker nanocrystal labeler with a fluorescent light one week after the surgery. Cells from the bone lineage were found among the labeled cells. The radiographic evaluations demonstrated a speed up in bone growth in dogs from G2 and G3, and significant differences were found between G1 and G3 dogs, in all studied periods; and between G1 and G2 animals at 30 and 45 days. The rhBMP-2 supplemented or not-supplemented adult MSC are favorable alternatives to the bone growth in the healing process of acute experimental-induced tibial defects in dogs.

Comparing progression of non-functioning pituitary adenomas in hypopituitarism patients with and without long-term GH replacement therapy.

OBJECTIVE: An important safety issue with GH replacement therapy (GHRT) in hypopituitary patients with a history of a pituitary adenoma is the risk for tumour recurrence or enlargement. Design Case-control study. SUBJECTS AND METHODS: We studied tumour progression rate in 121 patients with hypopituitarism on the basis of non-functioning pituitary adenomas (NFPA) receiving long-term GHRT. A group of 114 NFPA patients not receiving GHRT who were matched in terms of duration of follow-up, gender, age, age at diagnosis and radiotherapy status were used as a control population. The average duration of GHRT was 10+/-4 years (range 2-17). RESULTS: In patients with a known residual adenoma, 63% had no detectable enlargement of tumour during the study. In patients who had no visible residual tumour prior to GHRT, 90% did not suffer from recurrence. In total, the 10-year tumour progression-free survival rate in patients with NFPA receiving GHRT was 74%. In the control population not receiving GHRT, the 10-year progression-free survival rate was 70%. Radiotherapy as part of the initial tumour treatment reduced the rate of tumour progression in both GHRT and non-GHRT patients to a similar extent. CONCLUSIONS: The rate of tumour progression was similar in this large group of GHRT patients and the control population not receiving GHRT. Our results provide further support that long-term use of GH replacement in hypopituitarism may be considered safe in patients with residual pituitary adenomas.

Rapid thawing of fresh-frozen plasma with radio wave-based thawing technology and effects on coagulation factors during prolonged storage at 4 degrees C.

BACKGROUND AND OBJECTIVES: With traditional techniques the thawing time for fresh-frozen plasma (FFP) is about 20-30 min. A new technology using radio waves, radio wave thawing device (RTD), was applied for thawing FFP. With this technology the thawing time can substantially be reduced. The new technique was compared to an established method using Heated Air Technology (HAT). Variables subjected to assessment were temperature after thawing and analysis of factor V (FV), factor VIII (FVIII), protein S. MATERIALS AND METHODS: Plasma was collected from 20 plasma donors. Each donation was aliquoted into two equal units of approximately 250 ml. The plasma units were frozen and stored below -75 degrees C. The thawing time was pre-set to two time periods, one for each group, 23 min for HAT and 7.5 min for RTD. Thawed plasma was stored at 4 +/- 2 degrees C as liquid plasma. Samples were collected before freezing, after thawing, 1 week and 2 weeks after thawing. RESULTS: The FV and FVIII levels were over 90% direct after thawing compared to before freezing values in both groups. At 2 weeks of storage the levels of FV and FVIII were approximately 70% and 50%, respectively, compared to before freezing values. Protein S levels decreased slightly during storage. No significant differences in the decline of quality were observed between the two groups. CONCLUSION: The new radio wave technology for thawing of FFP has a significant reduction of thawing time. The impact of thawing and storage on FV, FVIII, protein S does not significantly differ between HAT and RTD.

Conjunctivitis outbreak among divers.

In March 2006, an outbreak of conjunctivitis that occurred over a six day period among twenty-nine individuals who partook in recreational scuba diving trips on two boats off Vitu Levu Island, Fiji. We investigated the likelihood that a communal container used to store diving masks facilitated the spread of conjunctivitis among individuals. The diagnosis of conjunctivitis was based on clinical assessment by a physician. Transmission of conjunctivitis from person to person was documented with eventual identification of the index case, the dive master, a Fijian resident. Topical antibiotics were dispensed accordingly and detergent and bleach were used as mask cleaning agents in an effort to control the outbreak. Follow up surveys were mailed to all twenty-nine participants. Ultimately, fourteen cases of conjunctivitis were documented (46.7%). Eleven cases were verified during the six days in Fiji, two upon arrival back in the U.S., and one case of familial transmission in the U.S. All but two cases resolved within one week. Unknown to these divers was a coincidental, generalized outbreak of acute haemorrhagic conjunctivitis among the Fijian Residents. The communal container used to store diving masks was the likely vector for the spread of infectious conjunctivitis, the first such documented outbreak involving communal diving equipment.

Combination therapy with interferon-beta and glatiramer acetate in multiple sclerosis.

OBJECTIVES: To compare the effects of mono-therapy with interferon-beta (IFN-beta) or glatiramer acetate (GA) with IFN-beta + GA combination therapy for persons with multiple sclerosis (MS). MATERIALS & METHODS: In the context of a longitudinal observational study at the MS Centre, Karolinska University Hospital, Huddinge, 83 persons with MS receiving mono-therapy at baseline were studied. Because of MS worsening 21 switched to IFN-beta + GA combination therapy for 16-24 months, and 62 remained on the same mono-therapy for 24 months. Multiple Sclerosis Functional Composite, cognitive function, depressed mood, relapse occurrence and perceived physical and psychological impact were assessed. Linear mixed-effects models and generalized estimating equations were employed to evaluate changes in each outcome over time. RESULTS: Patients on IFN-beta + GA therapy showed greater change in odds for high perceived psychological impact. No other significant differences between treatments were found. CONCLUSIONS: The results underline the need for a randomized trial of IFN-beta + GA in MS.

Violence from young women involuntarily admitted for severe drug abuse.

OBJECTIVE: To simultaneously evaluate actuarial and dynamic predictors of severe in-patient violence among women involuntarily admitted for severe drug abuse. METHOD: All patients admitted to special facilities for involuntary treatment of absconding-prone, previously violent, drug abusing women in Sweden were assessed with the Staff Observation Aggression Scale, revised. Actuarial data on risk factors for violence were collected and considered in an extended Cox proportional hazards model with multiple events and daily assessments of the Broset Violence Checklist as time-dependent covariates. RESULTS: Low-grade violence and being influenced by illicit drugs were the best predictors of severe violence within 24 h. Significant differences in risk for violence between different institutions were also found. CONCLUSION: In-patient violence risk is rapidly varying over time with being influenced by illicit drugs and exhibiting low-grade violence being significant dynamic predictors. Differences in violence between patients could not be explained by patient characteristics.

Nurses' short-term prediction of violence in acute psychiatric intensive care.

OBJECTIVE: To evaluate the short-term predictive capacity of the Brøset Violence Checklist (BVC) when used by nurses in a psychiatric intensive care unit. METHOD: Seventy-three patients were assessed according to the BVC three times daily. Violent incidents were recorded with the Staff Observation Aggression Scale, revised version. An extended Cox proportional hazards model with multiple events and time-dependent covariates was estimated to evaluate how the highest BVC sum of the last 24 h and its separate items affect the risk for severe violence within the next 24 h. RESULTS: With a BVC sum of one or more, hazard for severe violence was six times higher than if the sum was zero. Four of the six separate items significantly increased the risk for severe violence with hazard ratios between 3.0 and 6.3. CONCLUSION: Risk for in-patient violence in a short-term perspective can to a high degree be predicted by nurses using the BVC.

Emphysematous cystitis: rapid resolution of symptoms with hyperbaric treatment: a case report.

INTRODUCTION: Emphysematous cystitis is a rare disease that occurs most often in elderly diabetic patients characterized by gas formation in the bladder wall due to infection. The infecting organism is usually an aerobic bacterium, most commonly E. coli although anaerobic species have also been reported. We report the use of hyperbaric oxygen in a patient with emphysematous cystitis and air in the femoral vein in which the treatment rapidly resolved the symptoms and radiological abnormalities. METHODS: A 65-year-old female presented to the Emergency Department with altered mental status, weakness, dark urine, dysuria and fever. She was febrile and lethargic. Abdominal exam showed suprapubic tenderness. Urinalysis was positive for white blood cells and bacteria. A CT scan of the abdomen demonstrated extensive air in the bladder wall with an air bubble in the femoral vein. Presumptive diagnosis was urinary tract infection, emphysematous cystitis, and sepsis. A question of air embolism was raised due to the intravascular gas. The patient was treated with hyperbaric oxygen (2.85 atm abs, 90 minutes) on two separate occasions in the first 12 hours. Within 24 hours, the patient's condition rapidly improved. Repeat CT scan 48 hours after admission showed near complete resolution of the emphysematous cystitis. The patient grew Klebsiella pneumonia from her urine. CONCLUSIONS: Emphysematous cystitis is a rare condition caused by either aerobic or anaerobic bacteria and may be associated with both bladder wall and intravascular gas formation. Hyperbaric oxygen therapy has not been previously reported as a treatment modality. The rapid improvement in our patient may indicate a role for hyperbaric oxygen in addition to IV hydration and antibiotics in this disease.

A multisite survey of factors contributing to medically unnecessary ambulance transports.

OBJECTIVES: To determine the social and demographic factors associated with medically unnecessary ambulance utilization, and to determine the willingness of patients to use alternate modes of transportation to the ED. METHODS: A multisite prospective survey was conducted of all patients arriving by ambulance to 1 suburban and 4 urban EDs in New York State during a 1-week period. RESULTS: For 626 patients surveyed, 71 (11.3%) transports were judged medically unnecessary by the receiving emergency physicians using preestablished guidelines. The patient's type of medical insurance and age were significant predictors of unnecessary ambulance transport (stepwise forward logistic regression analysis). Of the 71 patients whose ambulance transports were deemed medically unnecessary, 42 (59%) were Medicaid recipients and 53 (74%) were < 40 years of age. The most common reason for using ambulance transport was lack of an alternate mode of transportation (38.5%), although 82% would have been willing to use an alternate mode of transportation if it had been available. Of those who had medically unnecessary ambulance use, 30% indicated that they would not pay for the ambulance service if billed and 50% believed the cost of their ambulance transports was < $100. More than 85% of the patients whose ambulance transports were deemed medically unnecessary were unemployed; and nearly 85% reported a net annual income of < $20,000. While 33% had a primary care provider, only 22% had attempted to contact their doctors before requesting an ambulance. CONCLUSIONS: Patient age < 40 years and Medicaid coverage were associated with medically unnecessary ambulance use. Those patients for whom ambulance use was considered medically unnecessary commonly had no alternate means of transportation. Providing alternate means of unscheduled transportation may reduce the incidence of unnecessary ambulance use.

Adrenal medullary implants in the dopamine-denervated rat striatum. II. Acute behavior as a function of graft amount and location and its modulation by neuroleptics.

Rotational behavior was studied in rats with unilateral 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine system, following intrastriatal grafting of pieces of the adrenal medulla or nervus opticus. The rats were placed in rotometers immediately after the operation. No rotational response was seen in animals implanted with nervus opticus. Rats that received one whole adrenal medullary gland, divided into 4 pieces, showed a strong rotational response with a peak after 100 min and a duration of 400 min. Adrenal medulla-induced rotations were dose-dependent: when rats were grafted with 2, 4 or 8 pieces (where 4 pieces equals one whole adrenal medulla) into 2 sites, 2 pieces induced about half the amount of rotation as 4 pieces, while 8 pieces caused a higher total number of rotations with the 100 min peak approximately doubled compared with rats that had received 4 pieces. The coordinates for the implantation site were also important determinants of the rotational behavior: 4 implantation sites were tested and it was shown that the most central site in the caudate caused the highest total amount of rotations. The rotational behavior could be blocked in a dose-dependent manner by the dopamine-receptor antagonists haloperidol and cis-flupenthixol given immediately after grafting. It is concluded that implantation of chromaffin tissue from the adrenal medulla into the unilaterally 6-hydroxydopamine-denervated striatum causes highly reproducible acute rotational responses that vary with the amount and location of the implanted tissue and that can be blocked by neuroleptics. Thus the experiments permit screening of areas within neostriatum that produce different rotational responses to chromaffin implants.(ABSTRACT TRUNCATED AT 250 WORDS)