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INTRODUCTION: Endometriosis is a chronic inflammatory disease that affectsâ¯â¼â¯10â¯% of women. A significant fraction of patients experience limited or no efficacy with current therapies. Tissue adjacent to endometriosis lesions often exhibits increased neurite and vascular density, suggesting that disease pathology involves neurotrophic activity and angiogenesis. OBJECTIVES: We aim to evaluate the potential for key tyrosine-kinase-receptor-coupled neurotrophic molecules to contribute to endometriosis-associated pain in mice. METHODS: Peritoneal fluid was collected from endometriosis patients undergoing surgery and the levels of NGF and VEGFR1 regulators (VEGFA, VEGFB, PLGF, and sVEGFR1) were quantified by ELISA. VEGFR1 regulator concentrations were used to calculate VEGFR1 occupancy. We used genetic depletion, neutralizing antibodies, and pharmacological approaches to specifically block neurotrophic ligands (NGF or BDNF) or receptors (VEGFR1, TRKs) in a murine model of endometriosis-associated pain. Endometriosis-associated pain was measured using von Frey filaments, quantification of spontaneous abdominal pain-related behavior, and thermal discomfort. Disease parameters were evaluated by lesion size and prevalence. To evaluate potential toxicity, we measured the effect of entrectinib dose and schedule on body weight, liver and kidney function, and bone structure (via micro-CT). RESULTS: We found that entrectinib (pan-Trk inhibitor) or anti-NGF treatments reduced evoked pain, spontaneous pain, and thermal discomfort. In contrast, even though calculated receptor occupancy revealed that VEGFR1 agonist levels are sufficient to support signaling, blocking VEGFR1 via antibody or tamoxifen-induced knockout did not reduce pain or lesion size in mice. Targeting BDNF-TrkB with an anti-BDNF antibody also proved ineffective. Notably, changing dosing schedule to once weekly eliminated entrectinib-induced bone-loss without decreasing efficacy against pain. CONCLUSIONS: This suggests NGF-TrkA signaling, but not BDNF-TrkB or VEGF-VEGFR1, mediates endometriosis-associated pain. Moreover, entrectinib blocks endometriosis-associated pain and reduces lesion sizes. Our results also indicated that entrectinib-like molecules are promising candidates for endometriosis treatment.
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Background: Female Reddit users frequently discussed potential causes of orgasm difficulties and its implications on mental health and relationships. Aim: This study aimed to evaluate the experiences of women discussing orgasms on the Internet site Reddit. We sought to qualitatively analyze the topics that arose in users' discussions to better understand the potential causes of orgasm difficulties and its implications on quality of life. Methods: Posts on the subreddit r/TwoXChromosomes containing the keywords "orgasm" and "climax" were included in the dataset. Posts and their associated comments were qualitatively analyzed using the grounded theory approach. Two independent researchers coded each thread to identify dominant themes and emergent concepts. Outcomes: The most frequently coded primary topics included: (1) orgasm (32.2% [n = 337]), (2) psychological (17.8% [n = 186]), (3) relationships (15.4% [n = 161]), and (4) treatment (10.7% [n = 112]). Results: Qualitative analysis of 107 threads and approximately 6300 comments resulted in 5 major categories: psychological aspect of orgasms, difficulty orgasming with partners, partners' responses to orgasmic dysfunction, types of orgasms, and treatments for orgasmic dysfunction. Preliminary themes included (1) the presence of an emotional component or history of trauma related to orgasmic difficulty, (2) difficulty orgasming with a partner regardless of ability to orgasm during masturbation and a variety of stimulation required to orgasm, (3) mixed partner responses to orgasmic dysfunction, (4) the definition of a normal orgasm, and (5) self-motivated treatment for orgasmic dysfunction, including clitoral stimulation devices and masturbation techniques. Notably, few posters discussed their orgasmic dysfunction with healthcare providers. Clinical Translation: The study reveals insights into the possible causes, psychosocial implications, and treatment of orgasm difficulties from a patient perspective, and can guide future research on female orgasms in a more precise, patient-oriented direction. Strengths and Limitations: The anonymous nature of the forum allowed for insight into sensitive topics related to female orgasms and sexual trauma. Limitations include the demographic distribution of Reddit users, which was primarily younger women in their 20s and 30s, which restricts generalizability. Conclusion: Reddit provides a medium for individuals with orgasm difficulties to discuss their experiences. Posts addressed users' inability to orgasm, their mental health and relationships, the stimulation required for orgasm, and treatments for orgasmic dysfunction. Interestingly, very few posts discussed healthcare, potentially suggesting that women do not classify their orgasmic dysfunction as a health issue.
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Coronavirus disease (COVID)-related misinformation is prevalent online, including on social media. The purpose of this study was to explore factors associated with user engagement with COVID-related misinformation on the social media platform, TikTok. A sample of TikTok videos associated with the hashtag #coronavirus was downloaded on September 20, 2020. Misinformation was evaluated on a scale (low, medium, and high) using a codebook developed by experts in infectious diseases. Multivariable modeling was used to evaluate factors associated with number of views and presence of user comments indicating intention to change behavior. One hundred and sixty-six TikTok videos were identified and reviewed. Moderate misinformation was present in 36 (22%) videos viewed a median of 6.8 million times (interquartile range [IQR] 3.6-16 million), and high-level misinformation was present in 11 (7%) videos viewed a median of 9.4 million times (IQR 5.1-18 million). After controlling for characteristics and content, videos containing moderate misinformation were less likely to generate a user response indicating intended behavior change. By contrast, videos containing high-level misinformation were less likely to be viewed but demonstrated a nonsignificant trend towards higher engagement among viewers. COVID-related misinformation is less frequently viewed on TikTok but more likely to engage viewers. Public health authorities can combat misinformation on social media by posting informative content of their own.
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BACKGROUND: The true prevalence of low sexual desire among women is disputed among researchers due to the complex nature and presentation of women's sexual problems. AIM: To qualitatively analyze the aspects of libido/sexual desire frequently discussed by Reddit users and compare them with the current understanding of female sexual well-being and sexual desire disorders. METHODS: By using the Reddit application programming interface, the TwoXChromosomes subreddit was queried for posts with the keywords libido and sex drive. Posts that were deleted or unrelated to themes of libido/sex drive were excluded. A total of 85 threads-63 queried from the keyword libido and 22 from sex drive-and approximately 2900 comments were qualitatively analyzed per the grounded theory approach. Five independent researchers read and coded each thread to identify dominant themes and emergent concepts. OUTCOMES: Outcomes of interest included codes related to sexual dysfunction, libido, orgasm, masturbation, types of sex, psychology, relationships, intimacy, treatment, medications, and health care. RESULTS: Posters were primarily heterosexual women in their 20s and 30s. The code categories with the highest frequency were relationships (22.7%, n = 272), libido (22.2%, n = 210), psychological (20.2%, n = 191), medications (7.29%, n = 69), and intimacy (6.0%, n = 57). Users frequently described a decrease in libido secondary to medications, particularly antidepressants and hormonal birth control. Many users discussed the challenges of navigating a relationship with low sexual desire and the resulting sexual distress. Posters described feelings of sadness, anxiety, and guilt due to their low desire. Additionally, users discussed the role that sex plays in relationships, whether as a way to develop intimacy between partners or to achieve orgasm. Finally, posters expressed dissatisfaction with health care addressing their concerns surrounding sexual desire. CLINICAL IMPLICATIONS: The study findings-namely, the impact of medications on sexual health, the interaction of sexual desire and mental health, and cited examples of inadequate sexual health care-can help guide sexual well-being research, diagnosis, and public policy. STRENGTHS AND LIMITATIONS: Using Reddit as a data source allowed for the analysis of women's experiences outside the preestablished concepts of female sexual desire. Limitations to the study include the potential for posts to be deleted by moderator guidelines, the young demographic distribution of Reddit users, and the popularity-based structure of subreddit threads. CONCLUSION: Our results emphasize the psychosocial aspects of sexual desire and the need to redefine sexual problems to encompass the complex nature of female sexual well-being.
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Libido , Sexual Dysfunctions, Psychological , Female , Humans , Surveys and Questionnaires , Sexual Behavior/psychology , Sexual Partners/psychology , Sexual Dysfunctions, Psychological/psychologyABSTRACT
The progression of cancer from localized to metastatic disease is the primary cause of morbidity and mortality. The interplay between the tumor and its microenvironment is the key driver in this process of tumor progression. In order for tumors to progress and metastasize they must reprogram the cells that make up the microenvironment to promote tumor growth and suppress endogenous defense systems, such as the immune and inflammatory response. We have previously demonstrated that stimulation of Tsp-1 in the tumor microenvironment (TME) potently inhibits tumor growth and progression. Here, we identify a novel tumor-mediated mechanism that represses the expression of Tsp-1 in the TME via secretion of the serine protease PRSS2. We demonstrate that PRSS2 represses Tsp-1, not via its enzymatic activity, but by binding to low-density lipoprotein receptor-related protein 1 (LRP1). These findings describe a hitherto undescribed activity for PRSS2 through binding to LRP1 and represent a potential therapeutic strategy to treat cancer by blocking the PRSS2-mediated repression of Tsp-1. Based on the ability of PRSS2 to reprogram the tumor microenvironment, this discovery could lead to the development of therapeutic agents that are indication agnostic.
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Neoplasms , Thrombospondin 1 , Humans , Thrombospondin 1/genetics , Thrombospondin 1/metabolism , Tumor Microenvironment/genetics , Neoplasms/genetics , Trypsin , TrypsinogenABSTRACT
OBJECTIVES: Describe patient-reported pain and function within 24 months of a pelvic fracture treated with posterior screw fixation and identify factors associated with increased pain. DESIGN: Prospective case series. SETTING: Academic trauma center. PATIENTS/INTERVENTION: Eighty-eight patients with adult pelvic fracture treated with sacroiliac or transiliac screws. MAIN OUTCOME MEASURES: Average pain measured with the Brief Pain Inventory (BPI); function measured with the Majeed Pelvic Outcome Score from 6 to 24 months postinjury. RESULTS: The mean pain from 6 to 24 months postinjury was 2.22 on the 10-point BPI scale (95% CI, 0.64-3.81). Sixty-nine patients (78.4%) reported mild to no pain at 6 months; 12 (13.6%) patients had severe pain. Two years after injury, 71 patients (80.6%) exhibited mild to no pain. Within 24 months of injury, the mean pelvic function was 71 on the 100-point Majeed scale (95% CI, 60-82). Half of the sample (n = 44) had good to excellent pelvis function by 6 months postinjury; 55 patients (62.5%) attained this level of function by 24 months. A history of chronic pain (1.31; 95% CI, 0.26-2.37; P = 0.02), initial fracture displacement (≥5 mm) (0.99; 95% CI, 0.23-1.69; P = 0.01), and socioeconomic deprivation (0.28; 95% CI, 0.11-0.44; P < 0.01) were significantly associated with increased pain. CONCLUSION: Our findings suggest that most patients with unstable pelvic ring fractures treated with posterior screw fixation achieve minimal to no pelvis pain and good to excellent pelvic function 6-24 months after injury. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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Fractures, Bone , Pelvic Bones , Adult , Bone Screws , Fracture Fixation, Internal/adverse effects , Fractures, Bone/complications , Fractures, Bone/surgery , Humans , Pain , Pelvic Bones/injuries , Pelvic Bones/surgery , Retrospective Studies , Treatment OutcomeABSTRACT
PURPOSE: Previous studies have shown an association between injury risk and strabismus in aged Medicare beneficiaries and children. The injury prevalence in strabismic children was 30% in a study of >10 million patients in the OptumLabs Data Warehouse. The purpose of this study was to determine whether strabismus surgery decreases the risk of injury. DESIGN: Retrospective cohort study. METHODS: The OptumLabs Data Warehouse is a deidentified, longitudinal health database that was queried for strabismic patients aged <19 years. The patients who underwent strabismus surgery were compared with those strabismic patients who did not undergo surgery for injury. Injury risk (fractures, musculoskeletal injuries, and head injuries) during their insurance enrollment was calculated in the nonsurgical patients after their first strabismus claim and compared with the risk in surgical patients postoperatively. RESULTS: There were 344,794 patients with strabismus. Surgery was performed in 26,459 (7.7%). Esotropia was the most common diagnosis (n = 181,195, 52.6%) followed by exotropia (n = 161,712, 46.9%) and hypertropia (n = 43,831, 12.7%). Within these groups, patients with hypertropia were significantly more likely to undergo surgery (24.2%) compared with patients with esotropia and exotropia (10.2% and 9.6%, respectively). Injuries were diagnosed after the first strabismus claim in 94,960 (29.8%) nonsurgical patients vs 5790 (21.9%) postsurgical patients (P < .001) with a mean follow-up of 4.3 ± 3.1 vs 3.8 ± 3.1 years, respectively. The adjusted hazard ratio for injuries was 0.85 (95% confidence interval [CI]: 0.83-0.87) for the risk of any injury after strabismus surgery. The hazard ratio was significantly decreased after surgery for each type of strabismus: esotropia (0.91, 95% CI: 0.88-0.94), exotropia (0.82, 95% CI: 0.80-0.85), and hypertropia (0.89, 95% CI: 0.85-0.93). DISCUSSION: Strabismus surgery was associated with a 15% decrease in the risk of physical injury over approximately 4 years of follow-up. Surgery may be a factor in decreasing injury risk in strabismic patients, particularly in exotropia. Given the large number of children with strabismus in the United States, further assessment of strategies such as strabismus surgery to reduce injuries in children with strabismus is needed.
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Esotropia , Exotropia , Strabismus , Aged , Child , Data Warehousing , Esotropia/surgery , Humans , Medicare , Oculomotor Muscles/surgery , Retrospective Studies , Strabismus/epidemiology , Strabismus/surgery , United States/epidemiologyABSTRACT
PURPOSE: To define the prevalence of medical eye disease diagnoses among children enrolled in commercial insurance plans in the United States and to evaluate differences among groups based on the US census region, race/ethnicity, and familial net worth. METHODS: : Retrospective study of de-identified claims data from the OptumLab® Data Warehouse (OLDW) between 2007 and 2018. All children (<19 years) in the OLDW with coverage were studied and those with a claim for a significant eye disease (strabismus, amblyopia, nystagmus or structural eye disorders) with minimum 6-months follow-up were studied. Baseline characteristics were extracted for the calculation of eye disease prevalence, including age, sex, race/ethnicity, region of residence, and family net worth. The prevalence of each type of eye disease was calculated among all children and by baseline characteristics. RESULTS: : 10,759,066 children met the study criteria. The presence of any significant eye diagnosis was 6.7%. Disease was diagnosed more often in whites (6.9%) than blacks (5.6%) and Hispanics (5.9%). The most common eye disease diagnosed was strabismus (3.2%) followed by amblyopia (1.5%). In the North-East region, there was a 10.6% prevalence of any significant eye disease diagnosis, whereas in the Mid-West, it was 7.4% followed by the South and West (5.9% and 5.3%, respectively) (p < .001). There was an increase in eye disease diagnoses with increasing income (5.5% in<$25,000 and 9.4% in >$500,000 household net worth groups, p > .001). CONCLUSION: : Diagnosis of significant eye diseases is relatively common in American children. The most common medical eye disease diagnosis is strabismus. Prevalence of eye disease diagnosis from claims data varies between geographical regions and different income groups. This may reflect differences in healthcare utilization rather than true disease prevalence.
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Amblyopia , Strabismus , Amblyopia/epidemiology , Child , Data Warehousing , Humans , Prevalence , Retrospective Studies , Strabismus/diagnosis , Strabismus/epidemiology , United States/epidemiologyABSTRACT
BACKGROUND: To evaluate how eye diseases affect the risk of injuries (fractures, musculoskeletal, head and eye injuries) in children and teens. METHODS: Claims from the OptumLabs Data Warehouse, a longitudinal deidentified commercial insurance claims database, were analyzed. Eligible subjects were aged <19 years at the time of their eye disease diagnosis, enrolled in the health plan between 2007 and 2018, and had >1 visit for >1 significant eye disease (strabismus, amblyopia, nystagmus, structural diseases), based on ICD9/10 codes. Controls were children in the same database who had no eye disease codes reported. Demographics and injury claims (fractures, musculoskeletal injuries, head injuries and eye injuries) were compared. RESULTS: The overall incidence of any subsequent physical injury (even into adulthood) was 29% in eye disease patients and 23% in controls (P < 0.001). After accounting for covariates, the hazard ratio for injury with any type of eye disease was 1.14 (95% CI, 1.13-1.15), 1.17 (95% CI, 1.16-1.18), 0.97 (95% CI, 0.96-0.98), and 1.63 (95% CI, 1.60-1.66) for musculoskeletal injuries, fractures, head injuries, and eye injuries, respectively. The eye disease with the highest adjusted injury risk was nystagmus (HR = 1.26; 95% CI, 1.23-1.28), followed by optic neuritis and pseudotumor cerebri (HR = 1.25). The eye diseases with the lowest risk included amblyopia, esotropia, and glaucoma (HR ≤ 1.06). CONCLUSIONS: There was an increased long-term risk of physical injury among children and teens with eye disease. The clinical significance of these small differences is unclear.
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Craniocerebral Trauma , Eye Injuries , Musculoskeletal System , Adolescent , Adult , Child , Craniocerebral Trauma/diagnosis , Craniocerebral Trauma/epidemiology , Data Warehousing , Eye Injuries/diagnosis , Eye Injuries/epidemiology , Humans , Musculoskeletal System/injuries , Physical Examination , Young AdultABSTRACT
Importance: For critically ill patients with advanced medical illnesses and poor prognoses, overuse of invasive intensive care unit (ICU) treatments may prolong suffering without benefit. Objective: To examine whether use of time-limited trials (TLTs) as the default care-planning approach for critically ill patients with advanced medical illnesses was associated with decreased duration and intensity of nonbeneficial ICU care. Design, Setting, and Participants: This prospective quality improvement study was conducted from June 1, 2017, to December 31, 2019, at the medical ICUs of 3 academic public hospitals in California. Patients at risk for nonbeneficial ICU treatments due to advanced medical illnesses were identified using categories from the Society of Critical Care Medicine guidelines for admission and triage. Interventions: Clinicians were trained to use TLTs as the default communication and care-planning approach in meetings with family and surrogate decision makers. Main Outcomes and Measures: Quality of family meetings (process measure) and ICU length of stay (clinical outcome measure). Results: A total of 209 patients were included (mean [SD] age, 63.6 [16.3] years; 127 men [60.8%]; 101 Hispanic patients [48.3%]), with 113 patients (54.1%) in the preintervention period and 96 patients (45.9%) in the postintervention period. Formal family meetings increased from 68 of 113 (60.2%) to 92 of 96 (95.8%) patients between the preintervention and postintervention periods (P < .01). Key components of family meetings, such as discussions of risks and benefits of ICU treatments (preintervention, 15 [34.9%] vs postintervention, 56 [94.9%]; P < .01), eliciting values and preferences of patients (20 [46.5%] vs 58 [98.3%]; P < .01), and identifying clinical markers of improvement (9 [20.9%] vs 52 [88.1%]; P < .01), were discussed more frequently after intervention. Median ICU length of stay was significantly reduced between preintervention and postintervention periods (8.7 [interquartile range (IQR), 5.7-18.3] days vs 7.4 [IQR, 5.2-11.5] days; P = .02). Hospital mortality was similar between the preintervention and postintervention periods (66 of 113 [58.4%] vs 56 of 96 [58.3%], respectively; P = .99). Invasive ICU procedures were used less frequently in the postintervention period (eg, mechanical ventilation preintervention, 97 [85.8%] vs postintervention, 70 [72.9%]; P = .02). Conclusions and Relevance: In this study, a quality improvement intervention that trained physicians to communicate and plan ICU care with family members of critically ill patients in the ICU using TLTs was associated with improved quality of family meetings and a reduced intensity and duration of ICU treatments. This study highlights a patient-centered approach for treating critically ill patients that may reduce nonbeneficial ICU care. Trial Registration: ClinicalTrials.gov Identifier: NCT04181294.
Subject(s)
Critical Care , Critical Illness/therapy , Intensive Care Units , Overtreatment , Adult , Aged , Aged, 80 and over , Female , Humans , Length of Stay , Male , Middle Aged , Patient Acceptance of Health Care , Quality Improvement , Respiration, Artificial , Time FactorsABSTRACT
Atropine and patching are standard treatments for amblyopia, but the prevalence of atropine therapy in the United States is unknown. This study used the OptumLabs Data Warehouse to evaluate pharmacy claims for topical atropine to evaluate the frequency of its treatment for amblyopia and to compare demographic factors in cohorts of amblyopic children who were and were not prescribed atropine. Overall, 55.2% of amblyopic children were prescribed atropine more than once. The children who were prescribed atropine had a higher likelihood of living in geographic regions in the South or Midwest.
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Amblyopia , Amblyopia/drug therapy , Atropine/therapeutic use , Child , Data Warehousing , Follow-Up Studies , Humans , Mydriatics , Sensory Deprivation , Treatment Outcome , Visual AcuityABSTRACT
BACKGROUND: The hybridizing field crickets, Gryllus firmus and Gryllus pennsylvanicus have several barriers that prevent gene flow between species. The behavioral pre-zygotic mating barrier, where males court conspecifics more intensely than heterospecifics, is important because by acting earlier in the life cycle it has the potential to prevent a larger fraction of hybridization. The mechanism behind such male mate preference is unknown. Here we investigate if the female cuticular hydrocarbon (CHC) profile could be the signal behind male courtship. RESULTS: While males of the two species display nearly identical CHC profiles, females have different, albeit overlapping profiles and some females (between 15 and 45%) of both species display a male-like profile distinct from profiles of typical females. We classified CHC females profile into three categories: G. firmus-like (F; including mainly G. firmus females), G. pennsylvanicus-like (P; including mainly G. pennsylvanicus females), and male-like (ML; including females of both species). Gryllus firmus males courted ML and F females more often and faster than they courted P females (p < 0.05). Gryllus pennsylvanicus males were slower to court than G. firmus males, but courted ML females more often (p < 0.05) than their own conspecific P females (no difference between P and F). Both males courted heterospecific ML females more often than other heterospecific females (p < 0.05, significant only for G. firmus males). CONCLUSIONS: Our results suggest that male mate preference is at least partially informed by female CHC profile and that ML females elicit high courtship behavior in both species. Since ML females exist in both species and are preferred over other heterospecific females, it is likely that this female type is responsible for most hybrid offspring production.
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Animal Scales/chemistry , Courtship , Gryllidae/physiology , Hybridization, Genetic/physiology , Hydrocarbons/analysis , Sexual Behavior, Animal/physiology , Animal Scales/metabolism , Animals , Female , Gryllidae/genetics , Hydrocarbons/metabolism , Male , Reproduction/physiologyABSTRACT
Since their development, dental implants have become one of the most common procedures to rehabilitate patients with single missing teeth or fully edentulous jaws. As implants become more mainstream, determining the factors that affect osseointegration is extremely important. Medical risk factors identified to negatively affect osseointegration include diabetes and osteoporosis. However, other systemic conditions and medications that interfere with wound healing have not been as widely investigated. The aim of this systematic review was to evaluate the effect of systemic disorders including diabetes and osteoporosis on implant osseointegration. The aim was also to evaluate the effect of other diseases, such as neurocognitive diseases, cardiovascular disease, human immunodeficiency virus (HIV), hypothyroidism, rheumatoid arthritis, and medications, such as selective serotonin reuptake inhibitors (SSRIs), proton pump inhibitors (PPIs), and antihypertensives. Although the literature does not demonstrate that diabetes negatively affects implant osseointegration, most studies focus on well-controlled diabetics and the use of prophylactic antibiotics. In addition, studies have shown increased long-term bone and soft tissue complications. For osteoporosis, recent studies and reviews also fail to demonstrate a lower osseointegration rate. However, caution must be exercised in these patients due to the risk for osteonecrosis of the jaws (ONJ), especially in patients with bone malignancies. There is also no direct evidence that patients with HIV, cardiovascular disease, neurologic disorders, hypothyroidism, or rheumatoid arthritis have a decreased rate of implant osseointegration. However, some preliminary evidence suggests that medications such as SSRIs or PPIs may have a negative effect on implant osseointegration. These studies are fairly recent and must be validated with continuous research. Moreover, disease control, concomitant medications, and other comorbidities complicate implant osseointegration and must guide our treatment approaches and clinical guidelines.