Cruciate ligament injury : crunching the numbers

Cruciate Ligament (CL) injury is a serious injury that occurs primarily during activities like soccer, handball, floorball, alpine skiing, etc. Patients are generally young and the injury often results in early discontinuation of activity and an early onset of osteoarthritis (OA). The optimal treatment of CL injury is under continuous debate, where surgical reconstruction is recommended for patients engaged in high-level sports. Non-surgical treatment is considered to have a satisfactory outcome in the general population. CL injuries are one of the most studied topics within the field of sports medicine. Over 20,000 articles have been published, however none of these studies have hitherto used a national register-based approach. The overall aim of this thesis was to study the incidence, treatment and long-term effects of patients with CL injury in Sweden using a register-based approach. The thesis includes four studies, each with a specific aim. The first aim was to calculate the incidence of CL injuries in the general population. Earlier studies have focused on patients at risk or on the reported cases in a smaller geographical setting. Thus, the incidence in the general population has been unknown. For a long time, an argument for CL reconstruction (CL-R) has been that it prevents development of post traumatic OA, however, studies investigating this have presented conflicting results. Therefore, the second aim of this thesis was to study if this argument could be proven using a register-based approach. The third aim was to study what impact socioeconomic status (SES) has on the choice of treatment for these injuries. For other conditions, higher SES has been associated with a higher access to and utilization of surgical treatments, but its effect on patients with CL injury has never been studied. The fourth aim was to study how choice of treatment for a CL injury influenced changes in SES. This approach to create a new alternative outcome for symptomatic surgical procedures is essential in the process to develop new tools and methods for personalized medicine. This thesis shows that the incidence of CL injury in Sweden is 78 per 100,000 inhabitants. More than 50% of the patients are younger than 30 years and 60% are males. Overall, 36% are treated with surgical reconstruction and this option was more common among younger patients. Preventing post-traumatic OA is not a valid argument for CL-R. On the contrary patients going through surgical reconstruction had a 22% increased risk of developing symptomatic OA compared with those treated non-operatively. Ten percent of the patients developed symptomatic OA, and a concomitant meniscus injury increased this risk threefold. Even though CL-R is done with the aim to create a stable knee, SES had a big impact on which treatment the patient was admitted to. Patients with university education had a 29% increased likelihood of undergoing CL-R compared with those who had not graduated from high-school. The choice of treatment did not significantly affect the salary of a patient five years after injury. However, this thesis presents a multivariate model for an alternative outcome for symptomatic surgery where individual variables, such as socioeconomic outcome variables, are considered. This sets the foundation for future studies about symptomatic surgery, and the creation of decision tools to offer a more personalized treatment

Register-based studies of hypospadias

Hypospadias is a common genital malformation ofcomplex origin. It is characterized by misplacement of the urethral orifice, proximal to the tip of the glans penis, and is most often accompanied by a cleaved prepuce and varying degrees of ventral penile curvature. The phenotype ranges from distal hypospadias, where the misplacement of the urethral orifice is small, to more proximal cases where the urethral orifice may be located in the perineum and lead to uncertain sex at birth. This thesis aims to elucidate aspects of the etiology, and increase the knowledge concerning the consequences of being born with hypospadias. All studies are based on information collected from national population-based Swedish registers, containing healthcare and demographic data. In Study I we investigated associated risk factors, in terms of parental and perinatal characteristics, and the prevalence of hypospadias. We found an increased prevalence of boys assigned with hypospadias during the late 20th century. Further, we found that boys born small for gestational age, as twins, as a result of ART, or by parents from greater Europe (excluding the Nordic countries) or Asia were at an increased risk of being registered with a diagnosis of hypospadias. The trend in prevalence was not attributable to temporal changes in the investigated risk factors. Study II highlighted the association between hypospadias and the neuromuscular disorder known as spinal-bulbar muscle atrophy (SBMA), for which the common denominator is a CAG repeat expansion in the androgen receptor (AR) gene. We described one clinical case; a boy born with proximal hypospadias who was found to have 42 CAG repeats in the AR gene, which is a mutation known to cause SBMA later in life. In Swedish health care registers we found four potential cases of SBMA and hypospadias in individuals and within families. In Study III we investigated socioeconomic outcomes in men born with hypospadias as a proxy of well-being in adulthood. We found that men born with hypospadias displayed a similar level of education and income, and were as likely to be married as non-affected men. Men with proximal hypospadias did, however, suffer a greater risk of receiving a disability pension. This risk may be due to the effect of unmeasured psychiatric comorbidity, conditions related to androgen deficiency, or hypospadias as a part of unrecognized syndromes. In Study IV we aimed to assess the fertility of adult men born with hypospadias. We found a lower probability of registered paternity among men with hypospadias; the association was most prominent in men with proximal hypospadias and of small magnitude in distal hypospadias. Men with hypospadias were more likely to being diagnosed with male infertility and of conceiving through ART. The overall results imply that fertility is impaired in men with distal and proximal hypospadias, probably as a result of anatomic features, gonadal dysfunction, psychological, or genetic factors

Enteral tube feeding of head and neck cancer patients undergoing definitive chemoradiotherapy in the Nordic Countries : Survey of the Scandinavian Society for Head and Neck Oncology

Purpose We assessed current policies and perceptions of enteral tube feeding in head and neck cancer (HNC) patients undergoing chemoradiotherapy (CRT). A web-based survey was used to compare the timing and method of tube feeding within and between the five Nordic countries, covering a population of 27 million. Methods From each of the 21 Nordic university hospitals, one oncologist and one otorhinolaryngology-head and neck (ORL-HN) surgeon responded to a survey. The respondents were asked whether tube insertion before the onset of CRT, or during CRT as required (prophylactic vs. reactive) was preferred. The use of a pretreatment nutritional screening tool and the choice of feeding route (nasogastric vs. gastrostomy tube) were assessed. In total, we analyzed responses from 21 oncologists and 21 ORL-HN surgeons. Results A tendency was observed towards decreasing the use of a PEG tube. Of the 21 university hospitals, only 2 (10%) reported using a prophylactic PEG tube in over half of HNC patients undergoing definitive CRT. The preferred method for reactive tube feeding was by a NG tube in 14 of 21 (67%), and by a PEG in 7 of 21 (33%). In general, both oncologists and ORL-HN surgeons were content with their current policy. Conclusions The practices for enteral tube feeding in HNC management vary within and between the Nordic countries. We suggest that unified protocols for tube feeding should be developed for this patient population.Peer reviewe

Hypospadias as a novel feature in spinal bulbar muscle atrophy

Spinal and bulbar muscle atrophy (SBMA) is an X-linked neuromuscular disorder caused by CAG repeat expansions in the androgen receptor (AR) gene. The SBMA phenotype consists of slowly progressive neuromuscular symptoms and undermasculinization features as the result of malfunction of the AR. The latter mainly includes gynecomastia and infertility. Hypospadias is also a feature of undermasculinization with an underdeveloped urethra and penis; it has not been described as part of the SBMA phenotype but has been suggested to be associated with a prolonged CAG repeat in the AR gene. This study includes the first epidemiologic description of the co-occurrence of hypospadias and SBMA in subjects and their male relatives in Swedish population-based health registers, as well as an additional clinical case. One boy with severe hypospadias was screened for mutations in the AR gene and was found to have 42 CAG repeats in it, which is in the full range of mutations causing SBMA later in life. We also detected a maximum of four cases displaying the combination of SBMA and hypospadias in our national register databases. This is the third case report with hypospadias in association with CAG repeat expansions in the AR gene in the full range known to cause SBMA later in life. Our findings suggest that hypospadias may be an under diagnosed feature of the SBMA phenotype and we propose that neurologists working with SBMA further investigate and report the true prevalence of hypospadias among patients with SBMA.Swedish Research Council, K2012-64X-14506-10-5Stockholm City CouncilFoundation Frimurare Barnhuset in StockholmSwedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM), 340-2013-5867Accepte

A population-based nationwide study of cruciate ligament injury in Sweden, 2001-2009: Incidence, treatment, and sex differences

Background: A few national cruciate ligament (CL) registers have been initiated with operative surveillance and outcome monitoring. No nationwide study describing CL injury has ever been done. Purpose: To study the incidence and characteristics of patients diagnosed with cruciate ligament injury in Sweden. Study Design: Descriptive epidemiology study. Methods: Data for all patients with a diagnosed CL injury between 2001 and 2009 were identified from the National Swedish Patient Register. Risk analysis and specific incidences were calculated according to age, sex, geographic region, and surgery. Results: A total number of 56,659 patients with CL injury were included in the study, and the overall incidence of CL injury in Sweden was 78 per 100,000 persons. Sixty percent of the patients were male. The mean age was 32 years (range, 1-98 years), and 50% of the cohort was younger than 30 years. There was an increased rate of injury among female patients younger than 20 years as compared with male patients in that age group. Among patients with CL injury, 36% underwent reconstructive surgery, with one-third of these performed within 1 year after injury. Among patients who underwent surgery, 59% were male; the mean age was 27 years (range, 5-89 years). Conclusion: This study defines the incidence of CL injury and also demonstrates sex differences in which men were more likely to sustain a CL injury, although female patients were injured at an earlier age. The findings in this study corroborate the results from recent surgical registers. Clinical Relevance: No data have hitherto been published including all patients with CL injury, treated both surgically and nonsurgically. Such baseline epidemiologic data are crucial to be able to validate and judge the generalizability of results from procedure registers and clinical studies. © 2012 The Author(s)

Exposure to oestrogen and risk of anastomotic leakage after colorectal cancer surgery - A clue to the different leak rates in men and women

Background Colorectal anastomotic leakage is consistently more common in men, regardless of tumour location. This fact is largely unexplained but might be a consequence of biological differences including hormonal exposure and not only related to anatomy. Methods This was a retrospective, nationwide registry-based observational study of post-menopausal women operated for colorectal cancer with an anastomosis between 2007 and 2016. Hormonal exposure before surgery, as defined by prescribed drugs affecting oestrogen levels, was related to postoperative anastomotic leakage, using mixed-effects logistic regression models with adjustment for confounding. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were derived. In addition, separate estimates according to tumour location were computed, and a sensitivity analysis excluding topical oestrogen hormone exposure was conducted. Results Some 16,535 post-menopausal women were included, of which 16.2% were exposed to drugs increasing oestrogen levels before surgery. In this exposed group compared to the unexposed, leak rates were 3.1 and 3.8%, respectively. After adjustment, a reduction of anastomotic leakage in the exposed group was detected (OR: 0.77; 95% CI: 0.59-0.99). This finding was largely attributed to the rectal cancer subgroup (OR: 0.55; 95% CI: 0.36-0.85), while the exclusion of topical oestrogen drugs further reduced the estimates of the main analysis (OR: 0.63; 95% CI: 0.38-1.02). Conclusions Anastomotic leakage rates are lower in women exposed to hormone replacement therapy before surgery for colorectal cancer, which might explain some of the difference in leak rates between men and women, especially regarding rectal cancer.Peer reviewe

Occupational risk variation of nasopharyngeal cancer in the Nordic countries

Background The aim of this study was to estimate occupational risk variation in the incidence of nasopharyngeal cancer (NPC) in a large population-based cohort of the Nordic Occupational Cancer (NOCCA) study. Methods This study is based on a cohort of almost 15 million persons from Denmark, Finland, Iceland, Norway and Sweden, with 2898 nasopharyngeal cancer cases diagnosed in 1961-2005. The data on occupations were gathered from population censuses and cancer data from the national cancer registries. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were estimated using the national NPC incidence rates as the reference. Results There were 1980 male and 918 female NPC patients. The highest SIRs of NPC were observed among male waiters (SIR 3.69, 95% CI 1.91-6.45) and cooks and stewards (SIR 2.24, 95% CI 1.16-3.91). Among women, launderers had the highest SIR of NPC (2.04, 95% CI 1.02-3.65). Significantly decreased SIRs were found among male farmers (SIR 0.79, 95% CI 0.68-0.92) and male textile workers (SIR 0.49, 95% CI 0.22-0.93). Conclusions This study suggests that NPC may be associated with several work-related exposure agents such as smoking, kitchen air pollution and solvents. In future, occupational exposure-risk relations should be studied to understand more about causality and to assess effective prevention strategies.Peer reviewe

Hypospadias and increased risk for neurodevelopmental disorders

BACKGROUND: Hypospadias (aberrant opening of the urethra on the underside of the penis) occurs in 1 per 300 newborn boys. It has been previously unknown whether this common malformation is associated with increased psychiatric morbidity later in life. Studies of individuals with hypospadias also provide an opportunity to examine whether difference in androgen signaling is related to neurodevelopmental disorders. To elucidate the mechanisms behind a possible association, we also studied psychiatric outcomes among brothers of the hypospadias patients. METHODS: Registry study within a national cohort of all 9,262 males with hypospadias and their 4,936 healthy brothers born in Sweden between 1973 and 2009. Patients with hypospadias and their brothers were matched with controls by year of birth and county. The following outcomes were evaluated (1) any psychiatric (2) psychotic, (3) mood, (4) anxiety, (5) eating, and (6) personality disorders, (7) substance misuse, (8) attention-deficit hyperactivity disorder (ADHD), (9) autism spectrum disorders (ASD), (10) intellectual disability, and (11) other behavioral/emotional disorders with onset in childhood. RESULTS: Patients with hypospadias were more likely to be diagnosed with intellectual disability (OR 3.2; 95% CI 2.8-3.8), ASD (1.4; 1.2-1.7), ADHD (1.5; 1.3-1.9), and behavioral/emotional disorders (1.4; 1.2-1.6) compared with the controls. Brothers of patients with hypospadias had an increased risk of ASD (1.6; 1.3-2.1) and other behavioral/emotional disorders with onset in childhood (1.2; 0.9-1.5) in comparison to siblings of healthy individuals. A slightly higher, although not statistically significant, risk was found for intellectual disability (1.3; 1.0-1.9). No relation between other psychiatric diagnosis and hypospadias was found. CONCLUSIONS: This is the first study to identify an increased risk for neurodevelopmental disorders in patients with hypospadias, as well as an increased risk for ASD in their brothers, suggesting a common familial (genetic and/or environmental) liability.The Swedish Research CouncilThe Polish Ministry of Science and Higher EducationAccepte

Validating surgical procedure codes for inflammatory bowel disease in the Swedish National Patient Register

Background About 50% of patients with Crohn’s disease (CD) and about 20% of those with ulcerative colitis (UC) undergo surgery at some point during the course of the disease. The diagnostic validity of the Swedish National Patient Register (NPR) has previously been shown to be high for inflammatory bowel disease (IBD), but there are little data on the validity of IBD-related surgical procedure codes. Methods Using patient chart data as the gold standard, surgical procedure codes registered between 1966 and 2014 in the NPR were abstracted and validated in 262 randomly selected patients with a medical diagnosis of IBD. Of these, 53 patients had reliable data about IBD-related surgery. The positive predictive value (PPV), sensitivity and specificity of the surgical procedure codes were calculated. Results In total, 158 surgical procedure codes were registered in the NPR. One hundred fifty-five of these, representing 60 different procedure codes, were also present in the patient charts and validated using a standardized form. Of the validated codes 153/155 were concordant with the patient charts, corresponding to a PPV of 96.8% (95%CI = 93.9–99.1). Stratified in abdominal, perianal and other surgery, the corresponding PPVs were 94.1% (95%CI = 88.7–98.6), 100% (95%CI = 100–100) and 98.1% (95%CI = 93.1–100), respectively. Of 164 surgical procedure codes in the validated patient charts, 155 were registered in the NPR, corresponding to a sensitivity of the surgical procedure codes of 94.5% (95%CI = 89.6–99.3). The specificity of the NPR was 98.5% (95%CI = 97.6–100). Conclusions Data on IBD-related surgical procedure codes are reliable, with the Swedish National Patient Register showing a high sensitivity and specificity for such surgery