Alpha- and Beta-thalassemia: Rapid Evidence Review.

Thalassemia is a group of autosomal recessive hemoglobinopathies affecting the production of normal alpha- or beta-globin chains that comprise hemoglobin. Ineffective production of alpha- or beta-globin chains may result in ineffective erythropoiesis, premature red blood cell destruction, and anemia. Chronic, severe anemia in patients with thalassemia may result in bone marrow expansion and extramedullary hematopoiesis. Thalassemia should be suspected in patients with microcytic anemia and normal or elevated ferritin levels. Hemoglobin electrophoresis may reveal common characteristics of different thalassemia subtypes, but genetic testing is required to confirm the diagnosis. Thalassemia is generally asymptomatic in trait and carrier states. Alpha-thalassemia major results in hydrops fetalis and is often fatal at birth. Beta-thalassemia major requires lifelong transfusions starting in early childhood (often before two years of age). Alpha- and beta-thalassemia intermedia have variable presentations based on gene mutation or deletion, with mild forms requiring only monitoring but more severe forms leading to symptomatic anemia and requiring transfusion. Treatment of thalassemia includes transfusions, iron chelation therapy to correct iron overload (from hemolytic anemia, intestinal iron absorption, and repeated transfusions), hydroxyurea, hematopoietic stem cell transplantation, and luspatercept. Thalassemia complications arise from bone marrow expansion, extramedullary hematopoiesis, and iron deposition in peripheral tissues. These complications include morbidities affecting the skeletal system, endocrine organs, heart, and liver. Life expectancy of those with thalassemia has improved dramatically over the past 50 years with increased availability of blood transfusions and iron chelation therapy, and improved iron overload monitoring. Genetic counseling and screening in high-risk populations can assist in reducing the prevalence of thalassemia.

Toilet Training: Common Questions and Answers.

Toilet training is a significant developmental milestone in early childhood. Most U.S. children achieve the physiologic, cognitive, and emotional development necessary for toilet training by 18 to 30 months of age. Markers of readiness for toilet training include being able to walk, put on and remove clothing, and follow parental instruction; expressive language; awareness of a full bladder or rectum; and demonstrated dissatisfaction with a soiled diaper. Other readiness cues include imitating toileting behavior, expressing desire to toilet, and demonstrating bladder or bowel control (staying dry through a nap or through the night). Physicians should provide anticipatory guidance to parents beginning at about 18 to 24 months of age, noting the signs of toilet training readiness, and setting realistic expectations for parents. Parents should be counseled that no training method is superior to another. Parents should choose a method that is best suited to them and their child, and the method should use positive reinforcement. Complications of toilet training include stool toileting refusal, stool withholding, encopresis, hiding to defecate, and enuresis. These problems typically resolve with time, although some may require further investigation and treatment. Medical comorbidities such as Down syndrome, autism spectrum disorder, and cerebral palsy reduce the likelihood of successfully attaining full toilet training and often require early consultation with occupational therapists, developmental pediatricians, or other subspecialists to aid in toilet training.

Testicular Cancer: Diagnosis and Treatment.

Testicular cancer is the most common solid tumor among males 15 to 34 years of age, with an estimated 8,850 new cases and 410 deaths during 2017 in the United States. With effective treatment, the overall five-year survival rate is 97%. Risk factors for testicular cancer include undescended testis (cryptorchidism), personal or family history of testicular cancer, age, ethnicity, and infertility. The U.S. Preventive Services Task Force recommends against routine screening in asymptomatic men. Men with symptoms should receive a complete history and physical examination. Scrotal ultrasonography is the preferred initial imaging study. If a solid intratesticular mass is discovered, orchiectomy is both diagnostic and therapeutic. Staging through chest radiography, chemistry panel, liver function tests, and tumor markers guides treatment. Active surveillance, chemotherapy, retroperitoneal lymph node dissection, and radiation therapy are treatment options following orchiectomy. For patients desiring future fertility, sperm banking should be discussed early in the course of treatment. Family physicians often play a role in the care of cancer survivors and should be familiar with monitoring for recurrence and future complications, including secondary malignant neoplasms, cardiovascular risk, and infertility and subfertility.

Lower Extremity Abnormalities in Children.

Leg and foot problems in childhood are common causes of parental concern. Rotational problems include intoeing and out-toeing. Intoeing is most common in infants and young children. Intoeing is caused by metatarsus adductus, internal tibial torsion, and femoral anteversion. Out-toeing is less common than intoeing and occurs more often in older children. Out-toeing is caused by external tibial torsion and femoral retroversion. Angular problems include genu varum (bowleg) and genu valgum (knock knee). With pes planus (flatfoot), the arch of the foot is usually flexible rather than rigid. A history and physical examination that include torsional profile tests and angular measurements are usually sufficient to evaluate patients with lower extremity abnormalities. Most children who present with lower extremity problems have normal rotational and angular findings (i.e., within two standard deviations of the mean). Lower extremity abnormalities that are within normal measurements resolve spontaneously as the child grows. Radiologic studies are not routinely required, except to exclude pathologic conditions. Orthotics are not beneficial. Orthopedic referral is often not necessary. Rarely, surgery is required in patients older than eight years who have severe deformities that cause dysfunction.

Diagnosis and Treatment of Gastroesophageal Reflux in Infants and Children.

Gastroesophageal reflux is defined as the passage of stomach contents into the esophagus with or without accompanied regurgitation (spitting up) and vomiting. It is a normal physiologic process that occurs throughout the day in infants and less often in children and adolescents. Gastroesophageal reflux disease (GERD) is reflux that causes troublesome symptoms or leads to medical complications. The diagnoses of gastroesophageal reflux and GERD are based on the history and physical examination. Diagnostic tests, such as endoscopy, barium study, multiple intraluminal impedance, and pH monitoring, are reserved for when there are atypical symptoms, warning signs, doubts about the diagnosis, or suspected complications or treatment failure. In infants, most regurgitation resolves by 12 months of age and does not require treatment. Reflux in infants may be treated with body position changes while awake, lower-volume feedings, thickening agents (i.e., rice cereal), antiregurgitant formula, extensively hydrolyzed or amino acid formulas, and, in breastfed infants, eliminating cow's milk and eggs from the mother's diet. Lifestyle changes to treat reflux in children and adolescents include sleeping position changes; weight loss; and avoiding smoking, alcohol, and late evening meals. Histamine H2 receptor antagonists and proton pump inhibitors are the principal medical therapies for GERD. They are effective in infants, based on low-quality evidence, and in children and adolescents, based on low- to moderate-quality evidence. Surgical treatment is available, but should be considered only when medical therapy is unsuccessful or is not tolerated.

Dyspareunia in women.

Dyspareunia is recurrent or persistent pain with sexual activity that causes marked distress or interpersonal conflict. It affects approximately 10% to 20% of U.S. women. Dyspareunia can have a significant impact on a woman's mental and physical health, body image, relationships with partners, and efforts to conceive. The patient history should be taken in a nonjudgmental way and progress from a general medical history to a focused sexual history. An educational pelvic examination allows the patient to participate by holding a mirror while the physician explains normal and abnormal findings. This examination can increase the patient's perception of control, improve self-image, and clarify findings and how they relate to discomfort. The history and physical examination are usually sufficient to make a specific diagnosis. Common diagnoses include provoked vulvodynia, inadequate lubrication, postpartum dyspareunia, and vaginal atrophy. Vaginismus may be identified as a contributing factor. Treatment is directed at the underlying cause of dyspareunia. Depending on the diagnosis, pelvic floor physical therapy, lubricants, or surgical intervention may be included in the treatment plan.

Enuresis in children: a case based approach.

Enuresis is defined as intermittent urinary incontinence during sleep in a child at least five years of age. Approximately 5% to 10% of all seven-year-olds have enuresis, and an estimated 5 to 7 million children in the United States have enuresis. The pathophysiology of primary nocturnal enuresis involves the inability to awaken from sleep in response to a full bladder, coupled with excessive nighttime urine production or a decreased functional capacity of the bladder. Initial evaluation should include a history, physical examination, and urinalysis. Several conditions, such as constipation, obstructive sleep apnea, diabetes mellitus, diabetes insipidus, chronic kidney disease, and psychiatric disorders, are associated with enuresis. If identified, these conditions should be evaluated and treated. Treatment of primary monosymptomatic enuresis (i.e., the only symptom is nocturnal bed-wetting in a child who has never been dry) begins with counseling the child and parents on effective behavioral modifications. First-line treatments for enuresis include bed alarm therapy and desmopressin. The choice of therapy is based on the child's age and nighttime voiding patterns, and the desires of the child and family. Referral to a pediatric urologist is indicated for children with primary enuresis refractory to standard and combination therapies, and for children with some secondary causes of enuresis, including urinary tract malformations, recurrent urinary tract infections, or neurologic disorders.